Which Tumor Suppressor Gene Plays an Important Role in Oncogenesis of Oral Cancer?

口腔領域癌の遺伝子学的解析はあまり行われていないため, 本稿では当科における癌抑制遺伝子異常の検索結果を用いて, 口腔癌においてどの遺伝子が重要な役割を果たしているのかを検討した。試料は, 口腔扁平上皮癌組織と, 同一症例の正常組織を用いた。RB遺伝子とWT遺伝子についてはサザンブロッティング法により, また, APC, P53, VHL, p15, p16, p18遺伝子についてはPCR-SSCP法および塩基配列決定法を用いて検索した。さらに, APC遺伝子についてはエクソン11のポリモルフィズムを利用したPCR-LOH分析をあわせて行った。以下に示す結果を得た。(1)APC遺伝子の点突然変異は8.3%, APC-LOHは informative 症例中の72.7%に認められた。(2)p16遺伝子とp18遺伝子の点突然変異はそれぞれ4.0%, 3.8%に認められた。p15遺伝子異常は認められなかった。(3)p53心遺伝子異常は7.7%に認められた。(4)WT遺伝子の部分欠失を6.5%に認めた。(5)RB遺伝子とVHL遺伝子の異常は認められなかった。以上の結果から, 種々の癌抑制遺伝子のうち, 特にAPC遺伝子が口腔扁平上皮癌発生に重要な役割を果たしていることが示唆された。Since there are few molecular biological studies on oral cancer, we evaluated genes which would play an important role in the oncogenesis of oral cancer based on our previous studies. To elucidate whether or not abnormalities of RB and WT genes could contribute to the development of oral squamous-cell carcinoma (SCC), genomic DNAs obtained from tumors and corresponding normal tissues were examined with Southern blotting. On the other hand, PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) and sequence analyses were performed to detect possible mutations of APC, VHL, p15, p16, p18 and p53. We also examined the tissue samples to detect loss of heterozygosity (LOH) at exon 11 of APC gene by PCR-LOH assay. We obtained the following results: (1) Point mutations of APC gene in tumor tissues were identified in 8.3(nil)atients with oral SCC, and PCR-LOH assay revealed LOH at exon 11 of APC gene in 72.71024720030f informative cases. (2) Point mutations of p16 and p18 genes were detected in 4.0-0x1.db55b085084p-148nd 3.80f oral SCC patients, respectively. However, no mutation of p15 gene was found. (3) Abnormalities of p53 gene were detected in 7.726725462457f all cases. (4) Southern blotting revealed partial deletions and rearrangements of WT gene in 6.50f the cases. (5) No abnormality of VHL and RB genes was detected in any of the cases. These results suggest that APC gene is most significantly associated with the development of human oral SCC among the known tumor suppressor genes

Validity assumptions for a multiple-choice test of medical knowledge with open-books and web access. A known groups comparison study.

Relatively little evidence about the validity threats in open-book multiple-choice tests exist. The aim of this study was to examine validity aspects relating to gener-alization, extrapolation and decision of a multiple-choice test of medical knowledge with aids (open-book and internet access). The theoretical framework was modern validity theory, and the study was designed as a ‘known groups com-parison’ study. Test performances of three known groups of test takers hypothe-sized to have different knowledge levels of the test content were compared, and analysis of pass/fail decisions was used to examine implications of decisions based on test scores. Results indicated that it was possible to discriminate between expert and non-expert test taker groups even with the access to aids. In contrast, an inde-fensible passing score was found to be the largest potential threat to test validity. Relatively little evidence about the validity threats in open-book multiple-choice tests exist. The aim of this study was to examine validity aspects relating to gener-alization, extrapolation and decision of a multiple-choice test of medical knowledge with aids (open-book and internet access). The theoretical framework was modern validity theory, and the study was designed as a ‘known groups com-parison’ study. Test performances of three known groups of test takers hypothe-sized to have different knowledge levels of the test content were compared, and analysis of pass/fail decisions was used to examine implications of decisions based on test scores. Results indicated that it was possible to discriminate between expert and non-expert test taker groups even with the access to aids. In contrast, an inde-fensible passing score was found to be the largest potential threat to test validity.&nbsp

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

En kvalitativ studie om å ta liv Hvilke faktorer påvirker soldatens vilje til å ta liv i militære operasjoner?

Oppgaven undersøker temaet å ta liv, og skal finne svar på hvilke faktorer som påvirker soldatens vilje til å ta liv i militære operasjoner. Oppgaven har gjennom en kvalitativ dokumentundersøkelse drøftet litteraturen innenfor temaet. Den utvalgte hovedlitteraturen består av Grossman (1995), Murray (2013) og Waaler, Monsen, Larsson og Nilsson (2018). Disse er valgt på bakgrunn av sin sentrale rolle innenfor temaet, de presenterer forskjellige argumenter og viser bredden av ulike teorier på en god måte. Våre funn viser at det er konkrete faktorer som spiller inn på soldatens vilje til å ta liv. Disse faktorene har både biologiske kjennetegn og er formet av sosiale konstruksjoner og relasjoner. Faktorene er oppsummert i form av en modell. Oppgaven viser at faktorene som påvirker soldatens vilje til å ta liv er: sosialt konstruert motstand mot å ta liv, avstand, utdanning, aggresjon, frykt, samhold og ledelse. Forfatternes anbefaling er at oppgaven blir brukt til å sjekke ut om faktorene i modellen har hold ved bruk av andre metoder, og videre se hvordan man kan implementere disse faktorene i utdanning av soldater