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著者人数: 69名 (所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 吉川, 真), Number of authors: 69 (Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS): Yoshikawa, Makoto), Accepted: 2019-02-14, 資料番号: SA1190045000

In December 2018, the main-belt asteroid (6478)~Gault was reported to display activity. Gault is an asteroid belonging to the Phocaea dynamical family and was not previously known to be active, nor was any other member of the Phocaea family. In this work we present the results of photometric and spectroscopic observations that commenced soon after the discovery of activity. We obtained observations over two apparitions to monitor its activity, rotation period, composition, and possible non-gravitational orbital evolution. We find that Gault has a rotation period of $P = 2.4929 \pm 0.0003$ hours with a lightcurve amplitude of $0.06$ magnitude. This short rotation period close to the spin barrier limit is consistent with Gault having a density no smaller than $\rho = 1.85$~g/cm$^3$ and its activity being triggered by the YORP spin-up mechanism. Analysis of the Gault phase curve over phase angles ranging from $0.4^{\circ}$ to $23.6^{\circ}$ provides an absolute magnitude of $H = 14.81 \pm 0.04$, $G1=0.25 \pm 0.07$, and $G2= 0.38 \pm 0.04$. Model fits to the phase curve find the surface regolith grain size constrained between 100-500 $\rm{\mu}$m. Using relations between the phase curve and albedo we determine that the geometrical albedo of Gault is $p_{\rm v} = 0.26 \pm 0.05$ corresponding to an equivalent diameter of $D = 2.8^{+0.4}_{-0.2}$ km. Our spectroscopic observations are all consistent with an ordinary chondrite-like composition (S, or Q-type in the Bus-DeMeo taxonomic classification). A search through archival photographic plate surveys found previously unidentified detections of Gault dating back to 1957 and 1958. Only the latter had been digitized, which we measured to nearly double the observation arc of Gault. Finally, we did not find any signal of activity during the 2020 apparition or non-gravitational effects on its orbit., Comment: 15 pages, 11 figures; Accepted in MNRAS

Closed and open surgical techniques are two different main approaches to surgical exposure of palatally displaced canines (PDCs). Because there is insufficient evidence to support one technique over the other, there is a need for randomized controlled trials.To compare surgery time, complications and patients' perceptions between closed and open surgical techniques in PDCs.The trial was a multicentre, randomized, controlled trial with two parallel groups randomly allocated in a 1:1 ratio.Study participants were 119 consecutive patients from 3 orthodontic centres, with PDCs planned for surgical exposure, randomly allocated according to a computer-generated randomization list, using concealed allocation. Full-thickness mucoperiosteal flap was raised, and bone covering the canine was removed in both interventions. In closed exposure, an attachment with a chain was bonded to the canine and the flap was sutured back with the chain penetrating the mucosa. In open exposure, a window of tissue around the tooth was removed and glass ionomer cement placed on the canine crown, to prevent gingival overgrowth during spontaneous eruption. Patient perceptions were assessed with two questionnaires, for the evening on the day of operation and 7 days post-surgery.It was not possible to blind either patients or care providers to the interventions. The outcome assessors were blinded and were unaware of patients' intervention group.Seventy-five girls and 44 boys, mean age 13.4 years (SD 1.46) participated in the study and got either of the interventions (closed exposure, n = 60; open exposure, n = 59). Surgery time did not differ significantly between the interventions. Complications though were more severe in bilateral cases and the patients experienced more pain and impairment in the open group.There were no statistically significant differences regarding surgery time between the groups. Postoperative complications were similar between the groups in unilateral PDCs, but more common in the open group in bilateral cases. More patients in the open group experienced pain and impairment compared to the closed group.Trial registration: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201.

Circulating tumor cells (CTCs) are able to predict outcome in patients with breast, colon and prostate cancer and appear to be promising biomarkers of pancreatic carcinoma. The aim of the present study was to demonstrate a statistically significant portal-arterial difference of CTCs during curative resection of periampullary cancer. A commercially available instrument (IsofluxR) was used to quantify blood content of CTC in 10 patients with periampullary cancer according to preoperative diagnostics. Portal and arterial blood samples (~8 ml each) were simultaneously collected intra-operatively following surgical dissection prior to division of the pancreas for tumor removal. Quantitative CTC analyses were performed according to standardized protocols for immune-magnetic enrichment of CTC. Flow cytometry was applied for qualitative evaluations of various CTC markers in 7 patients. There was a statistically significant difference in the number of CTCs collected in the portal blood [58±14 cells per 100 ml; mean ± standard error (SE)] vs. arterial blood [24±7 cells per 100 ml (SE), P

We present rotationally resolved spectroscopy of asteroid (93) Minerva using the Lowell Discovery Telescope with the Near-Infrared High Throughput Spectrograph (NIHTS). We obtained spectroscopy over ~34% of the asteroid's rotation period. Minerva has been shown to be spectrally similar to primitive carbonaceous chondrites (e.g., McAdam et al., 2018, Icarus 306, 32–49) indicating it has amorphous materials on its surface. The extent to which these materials appear over Minerva's surface could provide constraints on the asteroid's formation time and/or directly relate the asteroid to a chemical group of carbonaceous chondrite meteorites. Parent asteroids are thought to preserve primitive meteorites in either an outer shell of material or by avoiding parent body processing (e.g., accreting after the peak heat flux of 26Al or before the introduction of exogenous 26Al to the Solar System). These two scenarios are expected to have different properties: the no processing scenario produces an asteroid with a compositionally homogenous surface and interior while the outer shell scenario would have compositionally distinct surface and interior. Over the observed region, we report that Minerva's surface appears to have amorphous materials, potentially indicating a homogeneous surface. However, more data are needed to determine Minerva's compositional uniformity and which formation scenario is most appropriate.

In 2018, the near-Earth object (155140) 2005 UD (hereafter UD) experienced a close fly by of the Earth. We present results from an observational campaign involving photometric, spectroscopic, and polarimetric observations carried out across a wide range of phase angles (0.°7–88°). We also analyze archival NEOWISE observations. We report an absolute magnitude of H V = 17.51 ± 0.02 mag and an albedo of p V = 0.10 ± 0.02. UD has been dynamically linked to Phaethon due their similar orbital configurations. Assuming similar surface properties, we derived new estimates for the diameters of Phaethon and UD of D = 5.4 ± 0.5 km and D = 1.3 ± 0.1 km, respectively. Thermophysical modeling of NEOWISE data suggests a surface thermal inertia of and regolith grain size in the range of 0.9–10 mm for UD and grain sizes of 3–30 mm for Phaethon. The light curve of UD displays a symmetric shape with a reduced amplitude of Am(0) = 0.29 mag and increasing at a linear rate of 0.017 mag/° between phase angles of 0° and ∼25°. Little variation in light-curve morphology was observed throughout the apparition. Using light-curve inversion techniques, we obtained a sidereal rotation period P = 5.235 ± 0.005 hr. A search for rotational variation in spectroscopic and polarimetric properties yielded negative results within observational uncertainties of ∼10% μm−1 and ∼16%, respectively. In this work, we present new evidence that Phaethon and UD are similar in composition and surface properties, strengthening the arguments for a genetic relationship between these two objects.

Thermal infrared observations are the most effective way to measure asteroid diameter and albedo for a large number of near-Earth objects. Major surveys like NEOWISE, NEOSurvey, ExploreNEOs, and NEOLegacy find a small fraction of high albedo objects that do not have clear analogs in the current meteorite population. About 8% of Spitzer-observed near-Earth objects have nominal albedo solutions greater than 0.5. This may be a result of lightcurve variability leading to an incorrect estimate of diameter or inaccurate absolute visual magnitudes. For a sample of 23 high albedo NEOs we do not find that their shapes are significantly different from the McNeill et al. (2019) near-Earth object shape distribution. We performed a Monte Carlo analysis on 1505 near-Earth objects observed by Spitzer, sampling the visible and thermal fluxes of all targets to determine the likelihood of obtaining a high albedo erroneously. Implementing the McNeill shape distribution for near-Earth objects, we provide an upper-limit on the geometric albedo of 0.5+/-0.1 for the near-Earth population., 19 pages, accepted by the Astronomical Journal

Background Tumour stem cells are considered important to promote disease progression, recurrence and treatment resistance following chemotherapy in colon cancer. However, genomic analyses of colorectal cancer have mainly been performed on integrated tumour tissue consisting of several different cell types in addition to differentiated tumour cells. The purpose of the present study was to compare genomic alterations in two cell fractions enriched of CD133+ and CD133−/EpCAM+ cells, respectively, obtained from fresh intraoperative human tumour biopsies. Methods The tumour biopsies were fractionated into CD133+ and CD133−/EpCAM+ cells by immunomagnetic separation, confirmed by immunocytochemistry and Q-PCR. DNA were extracted and used for array comparative genome hybridization (aCGH) after whole genome amplification. Frozen tumour tissue biopsies were used for DNA/RNA extraction and Q-PCR analyses to check for DNA alterations detected in the cell fractions. Results The number and size of DNA alterations were equally distributed across the cell fractions; however, large deletions were detected on chromosome 1, 7 and 19 in CD133−/EpCAM+ cells. Deletions were frequent in both cell fractions and a deletion on chromosome 19p was confirmed in 90% of the patients. Conclusion Isolation of enriched cells derived from tumour tissue revealed mainly genomic deletions, which were not observed in tumour tissue DNA analyses. CD133+ cells were genetically heterogeneous among patients without any defined profile compared to CD133−/EpCAM+ cells. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3206-8) contains supplementary material, which is available to authorized users.

The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2) content have been associated with poor prognosis in patients with colorectal cancer (CRC). There is a strong correlation between COX-2 expression and PGE2 production in tissues from CRC patients, suggesting an important role for COX-2 on the regulation of PGE2 production. Previous studies by the present authors, where CRC patients were divided into high- or low-COX-2 expressing tumors, displayed important differences in the expression levels of several transcription factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral oncogene homolog B (FosB), which is a member of the activator protein-1 complex, was the highest upregulated transcription factor in patients with high expression levels of COX-2. The present study aimed to investigate the role of FosB on the COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later the messenger (m)RNA expression levels of COX-1 and COX-2, as well as the PGE2 content, were measured. The results indicated that FosB knockdown decreased the expression levels of COX-2 but did not affect the PGE2 content or the mRNA expression levels of COX-1. The present findings suggest an important role for FosB on the regulation of COX-2 expression, but no effect on the regulation of the PGE2 levels. In addition, the present results imply independent regulatory mechanisms for COX-2 expression and PGE2 content.

OBJECTIVES Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival. METHODS DNA was extracted from tumor tissue from 59 PDAC patients, analyzed for KRAS mutations, and hybridized to 180 K CGH + SNP microarrays and 450 K methylation arrays. Analyses were based on postoperative survival where less than 12 months was considered to be short survival and more than 18 months was considered long survival. RESULTS Ninety-three percent of the patients had KRAS mutations in tumor DNA. Great heterogeneity of whole genome DNA sequence alterations were observed among chromosomes within the patient materials. Specific DNA sequence alterations did not directly predict postoperative survival, although short survivors had significantly more and larger DNA amplifications (P < 0.006). Amplifications on chromosome 11 and 21 and deletions on chromosome 2 predicted short postoperative survival (P < 0.03). DNA methylation was not related to survival. CONCLUSIONS Highly variable genetic differences among DNA regions in PDAC tumors were demonstrated. Postoperative short survival was related to tumor sequence DNA alterations on chromosome 2, 11, and 21.

Context.Basaltic V-type asteroids play a crucial role in studies of Solar System evolution and planetesimal formation. Comprehensive studies of their physical, dynamical, and statistical properties provide insight into these processes. Thanks to wide surveys, currently there are numerous known V-type and putative V-type asteroids, allowing a detailed statistical analysis.Aims.Our main goal is to analyze I corrected for US language conventions in this paper the currently available large sample of V-type spin rates, to find signatures of the non-gravitational Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) effect among the different V-type populations, and to estimate the spin barrier and critical density for V-type asteroids. Our intention is to increase the pool of information about the intriguing V-types.Methods.We collected rotational periods from the literature for spectrally confirmed V-types, putative V-types, and Vesta family members. Through spectroscopic observations we confirmed their taxonomic type and verified the high confirmation rates of the putative V-types. We combined the collected periods with periods estimated in this manuscript and produced rotational frequency distributions. We determined the spin barrier in the frequency–light curve amplitude space for V-type asteroids.Results.We analyzed rotational periods of 536 asteroids in our sample. As expected, due to the small size of the objects analyzed, the frequency distributions for the Vesta family and the V-types outside the family are inconsistent with a Maxwellian shape. The Vesta family shows an excess of slow-rotators. V-types outside the family show an excess of both slow and fast rotators. Interestingly, we found that the population of V-types outside the Vesta family shows a significant excess of fast rotators compared to the Vesta family. The estimated critical density for V-type asteroids exceedsρc= 2.0 g cm−3, which surpasses the previous estimates.Conclusions.We demonstrated that V-type asteroids have been influenced by the thermal radiation YORP effect and that their critical spin rate is higher than for C-type asteroids. The population of V-types outside the Vesta family shows a significant excess of fast rotators compared to the Vesta family. We hypothesize that the objects that evolved from the Vesta family though the Yarkovsky drift are also more susceptible to the YORP effect. Objects for which YORP has not yet had enough time to act and those that are more YORP resistant will be left in the family, which explains the relatively small proportion of fast rotators being left. The YORP timescale must thus be similar to the migration timescale for those objects.

We present lightcurves and derive periods and amplitudes for a subset of 38 near earth objects (NEOs) observed at 4.5 microns with the IRAC camera on the the Spitzer Space Telescope, many of them having no previously reported rotation periods. This subset was chosen from about 1800 IRAC NEO observations as having obvious periodicity and significant amplitude. For objects where the period observed did not sample the full rotational period, we derived lower limits to these parameters based on sinusoidal fits. Lightcurve durations ranged from 42 to 544 minutes, with derived periods from 16 to 400 minutes. We discuss the effects of lightcurve variations on the thermal modeling used to derive diameters and albedos from Spitzer photometry. We find that both diameters and albedos derived from the lightcurve maxima and minima agree with our previously published results, even for extreme objects, showing the conservative nature of the thermal model uncertainties. We also evaluate the NEO rotation rates, sizes, and their cohesive strengths., Comment: 16 pages, 4 figures, 3 tables, to appear in the Astrophysical Journal Supplement Series

NIHTS is a first-generation instrument now in use on Lowell Observatory’s Discovery Channel Telescope. It is a nearinfrared prism spectrograph of the BASS design featuring high throughput and low dispersion that is intended for observations of faint solar system and astrophysical objects over the YJHK spectral range. An unusual feature is its ability to observe simultaneously with the Large Monolithic Imager, an optical CCD camera, by means of a dichroic fold mirror. This is particularly valuable for time-variable targets such as Kuiper Belt Objects, asteroids, exoplanet transits, and brown dwarfs. We describe its design details and performance both in the lab and on the telescope.

Background: Understanding why adolescents miss dental appointments is central to promoting people’s oral health into adulthood. Studies on non-attendant adolescents are rare. Method: Using information from a population-based survey of schoolchildren in &#214rebro County, Sweden, we aimed to find factors associated with adolescents’ dental non-attendance and to suggest a risk-factor model for non-attendance. The 2014 survey of all pupils in three grades (~ages 13, 15, and 17) in the county (N = 7399) had a response rate of 80%. The questionnaire asked 67 or 86 questions (depending on grade) on five components: socioeconomic conditions, quality of life, social relations, lifestyle and health (with two specific questions on dental care and oral health), social cohesion and social capital. Using a model based on risk factors identified in the literature, we used descriptive statistics, bivariate analyses, and logistic regressions to find associations between dental attendance and potential risk factors. Results: Youth were non-attendant (n = 171) and attendant (n = 4236). Strong associations were found between non-attendance being a boy, being born outside Sweden, and living with parents not in the labor market. Health and health behaviors such as consuming sweet drinks or foods every day and being overweight were also associated with non-attendance. A model for risk of non-attendance based on variables significant in the analysis is presented. Conclusions: This study shows a strong association between non-attendant behavior and sociodemographic factors and health behavior. It also adds knowledge of the increased vulnerability to non-attendance in adolescents having at least one disability and/or experience of critical life.

Preclinical data, and an increasing list of clinical investigations, show anti-inflammatory agents to favourably influence the biology of colorectal tumor. We have earlier reported on re-expression of activated immune cells after three days preoperative treatment of patients with colorectal carcinoma, randomized to receive oral NSAID (indomethacin or celebrex). Antisecretory prophylaxis (esomeprasol) was provided to all patients and served as sham treatment. Concomittant to MHC locus activation, Prominin1/CD133, a marker associated with stemness and poor prognosis in several solid tumors, was downregulated. The aim of the present study was to evaluate expression of additional regulators belonging to the stem cell niche, OCT4, SOX2 and BMP7, as well as some microRNAs, reported to act as tumor suppressors or oncomiRs. Peroperative tumor biopsies were analyzed by microarrays, quantitative real-time PCR and immunohistochemistry (IHC). The stem cell master regulator SOX2 was increased by NSAIDs (p

We present archival observations demonstrating that main belt asteroid (6478) Gault has an extensive history of comet-like activity. Outbursts have taken place during multiple epochs since 2013 and at distances extending as far as 2.68 au, nearly aphelion. (6478) Gault is a member of the predominately S-type (i.e., volatile-poor) Phocaea family; no other main belt object of this type has ever shown more than a single activity outburst. Furthermore, our data suggest that this is the longest duration of activity caused by a body spinning near the rotational breakup barrier. If activity is indeed unrelated to volatiles, as appears to be the case, (6478) Gault represents a new class of object, perpetually active due to rotational spin-up.

In the absence of dense photometry for a large population of Near Earth Objects (NEOs), the best method of obtaining a shape distribution comes from sparse photometry and partial lightcurves. We have used 867 partial lightcurves obtained by Spitzer to determine a shape distribution for sub-kilometre NEOs. From this data we find a best fit average elongation $\frac{b}{a}=0.72 \pm 0.08$. We compare this result with a shape distribution obtained from 1869 NEOs in the same size range observed by Pan-STARRS 1 and find the Spitzer-obtained elongation to be in excellent agreement with this PS1 value of $\frac{b}{a}=0.70 \pm 0.10$. These values are also in agreement with literature values for $1, Comment: 8 pages, 7 figures. Accepted to ApJ

Background: Sporadic colorectal tumors probably carry genetic alterations that may be related to familiar clusters according to risk loci visualized by SNP arrays on normal tissues. The aim of the present study was therefore to search for DNA regions (copy number variations, CNVs) as biomarkers associated to genetic susceptibility for early risk predictions of colorectal cancer. Such sequence alterations could provide additional information on phenotypic grouping of patients. Material and Methods: High resolution 105K oligonucleotide microarrays were used in search for CNV loci in DNA from tumor-free colon mucosa at primary operations for colon cancer in 60 unselected patients in comparison to DNA in buffy coat cells from 44 confirmed tumor-free and healthy blood donors. Array-detected CNVs were confirmed by Multiplex ligation-dependent probe amplification (MLPA). Results: A total number of 205 potential CNVs were present in DNA from colon mucosa. 184 (90%) of the 205 potential CNVs had been identified earlier in mucosa DNA from healthy individuals as reported to the Database of Genomic Variants. Remaining 21 (10%) CNVs were potentially novel sites. Two CNVs (3q23 and 10q21.1) were significantly related to colon cancer, but not confirmed in buffy coat DNA from the cancer patients. Conclusion: Our study reveals two CNVs that indicate increased risk for colon cancer; these DNA alterations may have been acquired by colon stem cells with subsequent appearance among epithelial mucosa cells. Impact: Certain mucosa CNV alterations may indicate individual susceptibility for malignant transformation in relationship to intestinal toxins and bacterial growth.

Aim: This study aimed to investigate the role of dental fear (DF) and other personal characteristics in relation to dental behaviour management problems (DBMP).Design: A study group of 230 patients ...

This study aimed to identify potential predictors of non-attendance among children and adolescents with dental behaviour management problems (DBMP). A group of 179 patients, 7.5-19 yr of age, was grouped into 56 'non-attenders' (discontinued treatment, missed appointments, or >or= 20% cancellations) and 123 'attenders'. In addition to data from an introductory interview and dental recordings, baseline data from psychometric measures of fear and other personal and parental characteristics were included in logistic regression analyses and tree-based modelling. The non-attenders had higher scores on impulsivity and sociability and lower socio-economic status (SES) than the attenders, and they lived more often in single-parent families. Logistic regression analyses and tree-based modelling point to SES and parental anxiety as important predictors for non-attendance within this group of children and adolescents. To predict, and possibly to prevent, non-attendance among children and adolescents referred for specialized dental care because of DBMP, we must consider their lives and family situations as well as their personal characteristics and oral health status. Further research should focus on whether the observed associations between non-attendance and factors such as personal characteristics, family and psychosocial factors, and previous dental experiences, also hold for those who remain in regular dental care.

Alterations in eicosanoid metabolism is well established in a variety of malignant tumors, particularly colorectal carcinoma. Recent studies in our laboratory have emphasized a role for EP subtype receptors in progression of colorectal cancer and disease specific mortality. Therefore, the aim of the present study was to extend our knowledge to include additional receptor expression (DP1, DP2, FP, IP, TP) for prostanoids (PGD2, TXA2, PGF2alpha, PGI2) in relationship to tumor stage, differentiation and progression of colorectal cancer.Total RNA from 62 tumors and adjacent normal colon tissue (n = 48) was extracted. Quantification of receptor expression was performed by realtime PCR and related to the expression of an appropriate housekeeping gene (GAPDH). Tumors were assessed according to Dukes A-D (stage I-IV).DP1, DP2, FP and IP receptor subtypes displayed significantly reduced overall expression in tumor tissue compared to normal colon tissue, while the TP receptor subtype showed significantly higher expression in tumor tissue. Overall expression of the prostanoid receptors in tumor tissue was not related to clinical indexes as tumor stage and tumor cell differentiation evaluated by multivariate analyses. Cultured colorectal cancer cell lines with low (HT-29) and high (HCA-7) intrinsic PGE2 production at confluent state did not express DP1 and IP receptor subtypes, but displayed low expression of DP2, FP and TP receptor subtypes.The results in the present study indicate imbalanced expression of prostanoid receptors in colorectal cancer compared to normal colon tissue without clear cut relationship to disease progression. Therefore, future studies should be performed on defined cells within the tumor tissue compartment determining whether any prostanoid receptor(s) is useful as a molecular target in treatment or prevention of colorectal cancer.

The importance of prostaglandins in tumor growth and progression is well recognized, including antineoplastic activities by cyclooxygenase (COX) inhibitors. Variation in treatment response to COX inhibition has questioned differences in expression of cell surface and nuclear membrane receptors among tumors with different disease progression. The purpose of this study was to evaluate whether EP(1-4) subtype, PPAR gamma receptor and COX-1/COX-2 expression in colorectal cancer are related to tumor-specific mortality. Reverse transcription-polymerase chain reaction and immunohistochemistry were used to demonstrate expression and protein appearance in tumor tissue compared with normal colon tissue. EP(1) and EP(2) subtype receptor protein was highly present in tumor cells, EP(3) occurred occasionally and EP(4) was not visible. PPAR gamma, EP(2) and EP(4) mRNA were significantly higher in normal colon tissue compared with tumor tissue, without any distinct relationship to Dukes A-D tumor stage. Multivariate analyses indicated that increased tumor tissue EP(2) and COX-2 expression predicted poor survival (p

Prostaglandin E2 (PGE2) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE2 receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE2-producing epithelial-like tumors. Tumor tissue and plasma were collected and used for analyses with gene expression microarrays and multiplex enzyme-linked immunosorbent assays. Tumor growth, acute phase reactions/systemic inflammation and the expression of interleukin-6 were reduced in EP2-knockout tumor-bearing mice. Several hundreds of genes displayed major changes of expression in the tumor tissue when grown in EP2-knockout mice. Such gene alterations involved several different cellular functions, including stemness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE2 signaling via host EP2 receptors affected a large number of different genes involved in tumor progression based on signaling between host stroma and tumor cells, which caused reduced tumor growth.

Background Cyclooxygenase (COX) and epidermal growth factor receptor (EGFR) activities promote progression of colorectal cancer. Combined treatment against these targets has not been more effective than single treatments alone. Therefore, our aim was to analyze relationships between COX and EGFR in peroperative colorectal tumor biopsies. Method Tumor and colon mucosa tissue were collected at primary intended curative operations in patients according to well-recognized statistical distributions of tumor stages in colorectal cancer. COX-1, COX-2 and EGFR content in tumor and colon mucosa tissue were quantified by western blot and Q-PCR. Results COX-2 protein appeared as two bands, one at 66 kDa in almost all tumor and mucosa samples and one at 74 kDa in 73% of the tumors and in 23% of the mucosa samples. Tumor COX-2 mRNA was not different from the content in mucosa samples, while COX-2 protein was increased in tumor tissue (p < 0.0003). A correlation between 74 kDa COX-2 protein and COX-2 mRNA occurred in tumor tissue, with significantly increasing COX-2 mRNA across tumor stages. EGFR mRNA content was lower in tumor tissue (p < 0.0001), while EGFR protein was similar in tumor and mucosa samples. COX-2 and EGFR proteins showed a positive correlation in mucosa, while a negative correlation occurred in tumor tissue. Tumor tissue with high COX-2 74 kDa protein lacked EGFR protein. Conclusion Our present results are compatible with the theory that COX-2 and EGFR signalling pathways are inversely related in colorectal cancer tissue. This may explain why combinatorial clinical treatments have been less rewarding.

This study aimed to identify potential predictors of non-attendance among children and adolescents with dental behaviour management problems (DBMP). A group of 179 patients, 7.5-19 yr of age, was grouped into 56 'non-attenders' (discontinued treatment, missed appointments, oror= 20% cancellations) and 123 'attenders'. In addition to data from an introductory interview and dental recordings, baseline data from psychometric measures of fear and other personal and parental characteristics were included in logistic regression analyses and tree-based modelling. The non-attenders had higher scores on impulsivity and sociability and lower socio-economic status (SES) than the attenders, and they lived more often in single-parent families. Logistic regression analyses and tree-based modelling point to SES and parental anxiety as important predictors for non-attendance within this group of children and adolescents. To predict, and possibly to prevent, non-attendance among children and adolescents referred for specialized dental care because of DBMP, we must consider their lives and family situations as well as their personal characteristics and oral health status. Further research should focus on whether the observed associations between non-attendance and factors such as personal characteristics, family and psychosocial factors, and previous dental experiences, also hold for those who remain in regular dental care.

This study aimed to investigate the role of dental fear (DF) and other personal characteristics in relation to dental behaviour management problems (DBMP).A study group of 230 patients (7.5-19 years old; 118 girls), referred because of DBMP, was compared to a reference group of 248 same-aged patients (142 girls) in ordinary dental care. Patients and their parents independently filled in questionnaires including measures of fear and anxiety, behavioural symptoms, temperamental reactivity, and emotion regulation.Study group patients referred because of DBMP differed from the reference group in all investigated aspects of personal characteristics. In the multivariate analyses, DF was the only variable with consistent discriminatory capacity through all age and gender subgroups. Aspects of anxiety, temperament, and behavioural symptoms contributed, but differently for different subgroups and at different levels of dental fear.Among older children and adolescents, DF deserves to be re-established as the single most important discriminating variable for DBMP at clearly lower scores than commonly used. Further research should focus on the different patterns of DBMP development, considering various personal characteristics that may trigger, maintain, or exacerbate young patients' vulnerability to DF and DBMP.

The primary aim of this thesis was to study dental fear, personal characteristics and psychosocial concomitants in relation to dental behaviour management problems (DBMP) and dental attendance. The study sample consisted of children (8-12 yrs) and adolescents (13-19 yrs) referred to the Specialized Paediatric Dental Clinic because of DBMP. They were compared to a reference group of same aged dental patients in ordinary dental care. A methodological study explored the Dental Subscale of the Children's Fear Survey Schedule (CFSS-DS) in terms of agreement between self and parental ratings and age- and gender-differentiated cut-off scores as compared to the commonly used. Baseline data on children's and adolescents' dental fear, psychosocial situation and everyday life, and personal characteristics were analysed according to a variable-based approach using logistic regression analyses and tree-based modelling of group differences. From the frequency of missed or/and cancelled appointments or interruption of dental treatment the group of referred children was separated into two groups (non-attendees vs. attendees). The differences between the groups were analysed using logistic regression analyses and tree-based modelling. It was found that children and adolescents referred because of DBMP differ in several ways from children and adolescents in ordinary dental care. These differences concerns dental fear, emotional and behavioural problems and temperamental aspects, as well as psychosocial concomitants. The results indicated an overall more negative and complex picture for the children and adolescents referred because of DBMP. The occurrence of single-parent families, child-parent separations, and professional support actions were clearly more frequent among patients referred because of DBMP. Dental fear was the only variable with consistent discriminatory capacity for DBMP through all age and gender subgroups. Aspects of anxiety, temperament, and behavioural symptoms contributed to the prediction of DBMP, but differently for different subgroups and at different levels of dental fear. A non-attending behaviour within the DBMP group was predicted by family factors and a temperamental profile indicating an out-going and somewhat impulsive personal profile. The results indicate further need to establish and validate age and gender differentiated cut-off scores and that self-rating on the CFSS-DS should complement parental ratings, since DF was the single best predictor of DBMP at clearly lower scores than commonly used. Avoidance may be seen as the extreme of DBMP, varying from irregular dental attendance to dropping out entirely from dental treatment. Therefore deeper knowledge and understanding of DBMP, will help the dental staff to meet and treat children and adolescents according to their individual need and act for the prevention of DBMP and irregular dental attendance.

The first aim of this methodological study was to investigate the agreement between self-ratings of Children's Fear Survey Schedule (CFSS-DS). The second aim was to explore using differentiated cut-off scores, and to compare these cut-off scores with those commonly used.Three different data collections included study groups (n = 497) of children and adolescents who had been referred to specialized pediatric dentistry clinics, and reference groups (n = 499) of dental patients and children rating the analyses were limited to the Östergötland sample (n = 210 + 228). Patients and their accompanying parents (mainly mothers) were asked to fill in the CFSS-DS independently. Cut-off scores on the CFSS-DS scale were determined using receiver-operating characteristic analysis; patient-parent agreement was illustrated with Bland-Altman plots.The patient-parent agreement was modest, particularly among those who were referred because of dental behaviour management problems (DBMP). Cut-off scores differentiated by age and gender, suggested by exploration according to two different methods, were with few exceptions clearly below the standard cut-off score.[corrected] The validity of parental ratings of their children dental fear should be questioned, particularly in high-fear populations. Self-ratings should, as far as possible, be used to complement parental ratings. One consequence of using the standard cut-off score is the risk of overlooking some patients needs for special attention. Further research is needed to establish and validate age-and gender-differentiated cut-off scores on the CFSS-DS.

Prostaglandins support progression of colorectal cancer by several mechanisms. This conclusion is based on epidemiological and drug intervention long-term studies or retrieved from animal and cell culture experiments. The aim of the present study was to map receptor and enzyme expression for prostanoid metabolism in the presence of high or low PGE2 content within colon cancer tissue at primary tumor operation and after short-term preoperative provision of non-steroidal anti-inflammatory drug (NSAID). Twenty-three unselected patients with colon cancer were randomly selected to receive indomethacin (NSAID) or sham treatment for 3 days before surgery. Normal colon and tumor tissue were collected at operation for RNA extraction. Tissue PGE2 levels were measured by radioimmunoassay. Gene expression was quantified by microarray and real-time PCR. COX-1 expression increased proportionally to COX-2 expression in colon cancer tissue from untreated patients. Indomethacin reduced PGE2 content in normal and tumor tissue with subsequently decreased IP, HPGD and PPARgamma receptor expression in both tumor and normal colon tissue, while subtype EP1-4 receptors were not significantly influenced by indomethacin treatment. MPGES-1 expression was not related to overall PGE2 content in tumor and colon tissue, but decreased significantly in normal tissue during indomethacin exposure. Reduction of tumor tissue PGE2 was related to significant alteration in expression of several hundred genes indicating decreased cell cycling and increased apoptosis during indomethacin treatment, probably related to upregulation of acute phase reactants in tumor tissue. Increased prostanoid activity in colon cancer tissue is related to cross-talk between tumor and stroma cells.

Strong associations are assumed between inflammation, cancer initiation, and tumor progression. Weight loss and cachexia predispose for early death in cancer disease. Usually, such cachexia conditions are characterized by systemic inflammation, which is easily monitored by increased blood levels of C-reactive protein and an elevated erythrocyte sedimentation rate. Hypothetically, eicosanoids or, more specifically, prostaglandins could be common mediators in the promotion of cancer cachexia and the fatigue syndrome. Consequently, prostaglandins, particularly prostaglandin E2, have been reported to involve the development of anorexia, altered resting energy expenditure, tumor neoangiogenesis, elevated whole-body fat and cell metabolism, as well as blood and circulatory homeostasis in progressive cancer disease.

Children with dental behavioural management problems (DBMP) form a heterogeneous group, where personal characteristics play significant roles. Attention to everyday life and family situation as additional background facets may help to better understand and treat these patients.This study describes everyday life and family situation in child/adolescent patients referred because of DBMP, as compared to patients in ordinary dental care.A study group of 230 referred patients (8-19 years old; 118 girls) was compared to a reference group of 248 same-aged patients (142 girls) without DBMP. Patients and parents were interviewed according to a semistructured protocol.Patients referred because of DBMP more often lived in low socioeconomic status families, had parents not living together, fewer leisure-time activities, and were assessed as doing worse in social interactions compared to the reference group. Half of the study group had personal professional support, and some had experienced interventions by the social authorities. Whether these findings apply also to children/adolescents with DBMP who are not referred to specialist care remains to study.Many children and adolescents referred because of DBMP have a burdensome life and family situation. This should be paid attention to in research and in clinical care.

The objectives were to study the progression rate of approximal caries in 14 to 19-year-old adolescents and to assess the influence of experience of previous caries as a predictor of caries progression during the following years. The study population comprised 100 adolescents, all 19 years old, randomly selected. In all, there were 93 adolescents included in the study, for whom all sets of bitewing radiographs from 14 up to and including the age of 19 were assessed with respect to approximal caries. It could be noted that 32% of the adolescents had had at least one bitewing examination every year from 14 to 19 years of age. At the age of 14, 38% of the males and 24% of the females were radiographically without any sign of caries lesions (caries-free). The median survival time of initial caries in the present study was >5 years, while for manifest caries it was 3.2 years. It was found that 37% of the surfaces with manifest caries in males and 18% of the corresponding surfaces in females were restored within a year. The results show that experience of previous caries does not seem to be a significant indicator and does not influence when the next radiographic examination should be performed. It is thus concluded that individualized bitewing examination is the exception rather than the rule.