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Isotalo, Anu. "Poliisien tulkintoja suostumuksesta ja seksuaaliväkivallasta nuorten seurustelusuhteissa." Janus Sosiaalipolitiikan ja sosiaalityön tutkimuksen aikakauslehti 30, no. 3 (2022): 269–88. http://dx.doi.org/10.30668/janus.114709.
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Artikkelissa tarkastellaan seksuaali- ja väkivaltarikosten esitutkinnassa työskennelleiden poliisien puhetapoja suostumuksesta ja sen määrittelystä nuorten seurustelusuhteisiin liittyneissä raiskausepäilyissä. Tutkimusaineisto koostuu kymmenestä puolistrukturoidusta ryhmähaastattelusta (n=21), joita on analysoitu hyödyntämällä diskurssianalyysia. Haastateltavien työkokemuksiin perustuvat näkökulmat keskittyivät nuoriin naisiin uhreina ja heidän poikaystäviinsä epäiltyinä tilanteissa, joissa ei ollut käytetty fyysistä väkivaltaa. Poliisit kuvasivat suostumuksen puuttumista uhrin suorana painostamisena tai ilman suoraa painostusta tapahtuneena yhdyntätilanteena, jonka tahdonvastaisuutta uhri ei ilmaissut tai jonka tahdonvastaisuuden hän ymmärsi jälkikäteen. Aineistosta identifioitiin kolme diskurssia, joita analysoitiin sen kannalta, miten niissä tuotettiin sukupuoleen ja nuoruuteen sekä uhrin ja epäillyn positioihin liittyviä jäsennyksiä. Nämä diskurssit nimettiin uhrisensitiiviseksi, nuoria naisia vastuuttavaksi ja nuoria miehiä puolustavaksi puhetavaksi.
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Ohara, Arisa, Haruhiko Machida, Hisae Shiga, Wataru Yamamura, and Kenichi Yokoyama. "Improved image quality of temporal bone CT with an ultrahigh-resolution CT scanner: clinical pilot studies." Japanese Journal of Radiology 38, no. 9 (2020): 878–83. http://dx.doi.org/10.1007/s11604-020-00987-5.
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Abstract Purpose Ultrahigh-resolution CT (UHRCT) with slice collimation of 0.25 mm × 160 and matrix size of 1024 × 1024 has become clinically available. We compared the image quality of temporal bone CT (TBCT) between UHRCT and conventional multidetector CT (MDCT). Materials and methods We retrospectively enrolled 20 patients who underwent TBCT by MDCT (matrix size, 512 × 512) and subsequently by UHRCT (matrix size, 1024 × 1024). Two independent reviewers subjectively graded delineation of normal stapes, oval window, facial nerve canal, incudostapedial joint, and tympanic tegmen. We also quantified image noise in the cerebellar hemisphere. Between MDCT and UHRCT, we compared mean subjective grades using the Wilcoxon signed-rank test and the image noise using paired t test. Results Grades were significantly higher with UHRCT than with MDCT for all the anatomies (P < 0.001), whereas noise was significantly higher with UHRCT than with MDCT (P = 0.002). Conclusion For TBCT, UHRCT shows better delineation of the fine anatomical structures compared with MDCT.
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Kim, Tae Ho, Jae Sang Han, Jae Hong Han, et al. "Assessing Agreement Between Upright and Supine Head Roll Tests for Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo." Korean Journal of Otorhinolaryngology-Head and Neck Surgery 65, no. 9 (2022): 497–502. http://dx.doi.org/10.3342/kjorl-hns.2022.00136.
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Background and Objectives The newly introduced upright head roll test (UHRT), which exploits head rotations in the roll plane with the patient in the upright sitting position, is a diagnostic maneuver for horizontal canal-benign paroxysmal positional vertigo (HC-BPPV). This study is designed to determine whether UHRT, compared to supine head roll test (SHRT), can more accurately diagnose HC-BPPV and determine the subtype of HC-BPPV.Subjects and Method A total of 455 video nystagmus tests performed between April 2019 to June 2021 were retrospectively reviewed, and 63 patients with direction-changing positional nystagmus at UHRT or SHRT were enrolled in this study. UHRT result was classified as negative (if no nystagmus was observed), positive incomplete (if nystagmus was detected in one side), and positive complete (if nystagmus was evoked in both side). The frequency of nystagmus is also included in our assessment. In addition, the results of 4 patients with bow and lean test (BLT) records on videonystagmography were also analysed.Results The concordance rate between UHRT and SHRT was 97.8%, and the positive concordance rate was 91.38%. UHRT and SHRT provided identical subtype diagnosis in 98.1% (52 of 53 cases). In one case, UHRT and SHRT showed opposite results. Evaluating the affected side with bow and lean records, the SHRT, UHRT and BLT showed consistent results. The mean frequency of nystagmus was faster in SHRT than in UHRT.Conclusion UHRT showed equivalent results to SHRT in distinguishing subtype of HC-BPPV. UHRT is a useful method in diagnosing HC-BPPV simply in a sitting position.
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Koyanagi, Masamichi, Mitsuru Suzuki, Satoshi Kikuyama, et al. "NI-22 IMPROVED DELINEATION OF THE SUPERFICIAL CEREBRAL VENOUS SYSTEM IN BRAIN CT ANGIOGRAPHY BY ULTRAHIGH-RESOLUTION CT FOR ASSISTING BRAIN TUMOR SURGERY." Neuro-Oncology Advances 1, Supplement_2 (2019): ii29. http://dx.doi.org/10.1093/noajnl/vdz039.132.
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Abstract BACKGROUND In brain CT angiography (CTA) for assisting brain tumor surgery, delineation of the superficial cerebral venous system is critical for selecting the optimal surgical approach. This delineation is, however, limited using conventional CT scanners, including an area-detector CT (ADCT) scanner, due to their insufficient spatial resolution. Since March 2017, a state-of-the-art ultrahigh-resolution CT (UHRCT) scanner has been clinically available to improve in- and through-plane spatial resolution compared with conventional CT scanners, mainly due to smaller slice thickness from 0.5 mm to 0.25 mm, larger channel number from 896 to 1792, and smaller x-ray focus from 0.9 x 0.8 mm to 0.4 x 0.5 mm.PurposeWe assessed usefulness of UHRCT to improve delineation of the superficial cerebral venous system in brain CTA for assisting brain tumor surgery compared with conventional ADCT. METHODS We retrospectively enrolled patients with intra- and/or extra-axial brain tumors who underwent preoperative brain CTA for assisting brain tumor surgery by UHRCT or ADCT using our routine technique and generated the CTA to delineate the superficial cerebral venous system using the same technique. Two reviewers by consensus subjectively counted the number of the superficial sylvian veins and the cortical veins draining into these veins and the maximal bifurcation order of the cortical veins draining into the superior sagittal sinus. We compared these numbers and the maximal bifurcation order in the CTA between the UHRCT and ADCT groups using the intraoperative findings as the reference. RESULTS The numbers and the maximal bifurcation order in the UHRCT group were significantly greater and more accurate than those in the ADCT group. CONCLUSIONS Use of UHRCT can be clinically useful for better delineating the superficial cerebral venous system in brain CTA and assisting brain tumor surgery.
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Saito, Kuniaki, Keiichi Kobayashi, Shohei Iijima, et al. "NI-23 ULTRA-HIGH-RESOLUTION CT ANGIOGRAPHY FOR BRAIN TUMOR SURGERY." Neuro-Oncology Advances 1, Supplement_2 (2019): ii29—ii30. http://dx.doi.org/10.1093/noajnl/vdz039.133.
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Abstract BACKGROUND Preoperative accurate evaluation of arteries and veins can help avoid ischemic complication of brain tumor surgery. The latest ultra-high-resolution CT (UHRCT) angiography (Aquilion PrecisionTM; Canon Medical Systems) has recently become available for clinical testing of the main arteries and critical perforating arteries by brain CTA, compared to conventional CT. METHODS UHRCT provides slice collimation of 0.25 mm x 160 and matrix size of 1024 x 1024 or 2048 x 2048. Major features of this CT scanner include an improved detector system (the minimal slice thickness, 0.25 mm; the maximal channel number, 1792) and a small x-ray focus (the smallest size, 0.4 x 0.5 mm) compared to a standard multi-detector CT (MDCT) scanner (the minimal slice thickness, 0.5 mm; the maximal channel number, 896; the smallest x-ray focus size, 0.8 x 0.9 mm). RESULTS Until July 2019, 168 patients with brain tumor underwent UHRCT angiography. As high resolution image could visualize cortical arteries and cortical veins clearly, it helped to decide approach route to the tumor and achieve accurate biopsy of even small lesion. Identification of tumor feeders and passing arteries allowed for efficient feeder coagulation and preservation of passing artery, avoiding the ischemic change of surrounding brain. Improved image reconstruction could visualize perforating arteries, which helped to preserve perforator by predicting the location during tumor removal. CONCLUSION UHRCT angiography can visualize even tiny arteries and veins around the tumor, and contributes to avoid the risk of ischemic complication.
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Danilevskii, Rostislav Iurievich. "THE FIRST MONOGRAPH ON FRIEDRICH RUCKERT’S RUSSIAN RELATIONS." Russkaya literatura 3 (2021): 262–63. http://dx.doi.org/10.31860/0131-6095-2021-3-262-263.
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Nishikawa, Makiko, Haruhiko Machida, Yuta Shimizu, et al. "Image quality and radiologists’ subjective acceptance using model-based iterative and deep learning reconstructions as adjuncts to ultrahigh-resolution CT in low-dose contrast-enhanced abdominopelvic CT: phantom and clinical pilot studies." Abdominal Radiology 47, no. 2 (2021): 891–902. http://dx.doi.org/10.1007/s00261-021-03373-5.
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Abstract Purpose In contrast-enhanced abdominopelvic CT (CE-APCT) for oncologic follow-up, ultrahigh-resolution CT (UHRCT) may improve depiction of fine lesions and low-dose scans are desirable for minimizing the potential adverse effects by ionizing radiation. We compared image quality and radiologists’ acceptance of model-based iterative (MBIR) and deep learning (DLR) reconstructions of low-dose CE-APCT by UHRCT. Methods Using our high-resolution (matrix size: 1024) and low-dose (tube voltage 100 kV; noise index: 20–40 HU) protocol, we scanned phantoms to compare the modulation transfer function and noise power spectrum between MBIR and DLR and assessed findings in 36 consecutive patients who underwent CE-APCT (noise index: 35 HU; mean CTDIvol: 4.2 ± 1.6 mGy) by UHRCT. We used paired t-test to compare objective noise and contrast-to-noise ratio (CNR) and Wilcoxon signed-rank test to compare radiologists’ subjective acceptance regarding noise, image texture and appearance, and diagnostic confidence between MBIR and DLR using our routine protocol (matrix size: 512; tube voltage: 120 kV; noise index: 15 HU) for reference. Results Phantom studies demonstrated higher spatial resolution and lower low-frequency noise by DLR than MBIR at equal doses. Clinical studies indicated significantly worse objective noise, CNR, and subjective noise by DLR than MBIR, but other subjective characteristics were better (P < 0.001 for all). Compared with the routine protocol, subjective noise was similar or better by DLR, and other subjective characteristics were similar or worse by MBIR. Conclusion Image quality, except regarding noise characteristics, and acceptance by radiologists were better by DLR than MBIR in low-dose CE-APCT by UHRCT. Graphical abstract
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Yazdandoost, Farzaneh. "Emotion in Animated Films, Mieke Uhrig (ed.) (2018)." Animation Practice, Process & Production 10, no. 1 (2021): 143–49. http://dx.doi.org/10.1386/ap3_000030_5.
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Adachi, Takuya, Haruhiko Machida, Makiko Nishikawa, et al. "Improved delineation of CT virtual bronchoscopy by ultrahigh-resolution CT: comparison among different reconstruction parameters." Japanese Journal of Radiology 38, no. 9 (2020): 884–89. http://dx.doi.org/10.1007/s11604-020-00972-y.
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Abstract Purpose We compared the maximal recognizable bronchial bifurcation order (MRBBO) in CT virtual bronchoscopy (CTVB) using ultrahigh-resolution CT (UHRCT) and different reconstruction parameters. Materials and methods We enrolled 38 patients undergoing noncontrast chest CT by UHRCT and reconstructed CTVB utilizing 3 different combinations of reconstruction parameters, as classified into Group A (matrix size, 512; slice thickness, 1.0 mm), Group B (matrix size, 512; slice thickness, 0.5 mm), and Group C (matrix size, 1024; slice thickness, 0.25 mm). In right S1, left S1 + 2, and both S3 and S10, two reviewers counted the number of consecutively identified bronchial bifurcations to compare MRBBO among these groups using Kruskal–Wallis test. Results In these segments, MRBBO increased from Group A to C. MRBBO was significantly higher in Group C than in both Groups A and B in all the segments except left S10 (P < 0.05 for all). In left S10, it was significantly higher in Group C than in Group A (P < 0.05) but comparable between Groups B and C (P = 0.122). Conclusions MRBBO is higher in CTVB by UHRCT utilizing 1024-matrix size and 0.25-mm thickness than parameters currently recommended for CTVB (matrix size, 512; slice thickness, 0.5–1.0 mm).
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Mitchell, Bruce C., Jayajit Chakraborty, and Pratyusha Basu. "Social Inequities in Urban Heat and Greenspace: Analyzing Climate Justice in Delhi, India." International Journal of Environmental Research and Public Health 18, no. 9 (2021): 4800. http://dx.doi.org/10.3390/ijerph18094800.
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Climate change and rapid urbanization currently pose major challenges for equitable development in megacities of the Global South, such as Delhi, India. This study considers how urban social inequities are distributed in terms of burdens and benefits by quantifying exposure through an urban heat risk index (UHRI), and proximity to greenspace through the normalized difference vegetation index (NDVI), at the ward level in Delhi. Landsat derived remote sensing imagery for May and September 2011 is used in a sensitivity analysis of varying seasonal exposure. Multivariable models based on generalized estimating equations (GEEs) reveal significant statistical associations (p < 0.05) between UHRI/NDVI and several indicators of social vulnerability. For example, the proportions of children (β = 0.922, p = 0.024) and agricultural workers (β = 0.394, p = 0.016) are positively associated with the May UHRI, while the proportions of households with assets (β = −1.978, p = 0.017) and households with electricity (β = −0.605, p = 0.010) are negatively associated with the May UHRI. In contrast, the proportions of children (β = 0.001, p = 0.633) and agricultural workers (β = 0.002, p = 0.356) are not significantly associated with the May NDVI, while the proportions of households with assets (β = 0.013, p = 0.010) and those with electricity (β = 0.008, p = 0.006) are positively associated with the May NDVI. Our findings emphasize the need for future research and policies to consider how socially vulnerable groups are inequitably exposed to the impact of climate change-related urban heat without the mitigating effects of greenspace.
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Amirav, I., S. S. Kramer, M. M. Grunstein, and E. A. Hoffman. "Assessment of methacholine-induced airway constriction by ultrafast high-resolution computed tomography." Journal of Applied Physiology 75, no. 5 (1993): 2239–50. http://dx.doi.org/10.1152/jappl.1993.75.5.2239.
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Assessment of changes in airway dimensions during bronchoconstriction is conventionally based on measurements of respiratory mechanics. We evaluated the efficacy of ultrafast high-resolution computed tomography (UHRCT) to directly determine the dynamic changes in cross-sectional area (CSA) of airways in response to methacholine (MCh). UHRCT scans were obtained at functional residual capacity before (baseline) and after intravenous bolus injections of MCh (10(-8.5)-10(-7.0) mol/kg) to seven mechanically ventilated pigs. Changes in CSA of bronchi of varying baseline size (1–10 mm diam) were determined by using a customized image processing software package (VIDA) based on a user-directed computer-adjusted edge-finding algorithm. MCh induced dose-dependent decreases in CSA, which were paralleled by increases in airway opening pressure at higher doses of MCh; at lower doses of MCh, decreases in CSA of smaller airways were detected without concomitant changes in airway opening pressure. Changes in CSA were heterogeneous and variable, especially in the smaller airway ranges. The results of the present study support the concept that UHRCT can be used in conjunction with bolus challenges to effectively determine dose-response changes in airway caliber in both large and small airways. This technique provides data that may not be reflected by conventional lung function measurements and, hence, is a useful tool to study airway reactivity.
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Lilleby, Oscar, Peter Meidahl Petersen, Gedske Daugaard, and Katharina Anne Perell. "Current evidence for moderate and ultra-hypofractionated radiation therapy in prostate cancer: a summary of the results from phase 3 randomised trials." Scandinavian Journal of Urology 58 (June 20, 2023): 21–27. http://dx.doi.org/10.2340/sju.v58.7719.
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Problem: A low α/β ratio for prostate cancer (PCa) compared to surrounding normal tissue theoretically implies therapeutical advantages with hypofractionated treatment. Data from large randomised control trials (RCTs) comparing moderate hypofractionated (MHRT, 2.4–3.4 Gray/fraction (Gy/fx)) and ultra-hypofractionated (UHRT, >5 Gy/fx) with conventionally fractionated radiation therapy (CFRT, 1.8–2 Gy/fx) and the possible clinical implications have been reviewed.Materials and method: We searched PubMed, Cochrane and Scopus for RCT comparing MHRT/UHRT with CFRT treatment of locally and/or locally advanced (N0M0) PCa. We found six RCTs, which compared different radiation therapy regimes. Tumour control and acute and late toxicities are reported.Results: MHRT was non-inferior to CFRT for intermediate-risk PCa, non-inferior for low-risk PCa and not superior in terms of tumour control for high-risk PCa. Acute toxicity rates were increased compared to CFRT, especially an increase in acute gastrointestinal adverse effects was seen. Late toxicity related to MHRT seems to be comparable. UHRT was non-inferior in terms of tumour control in one RCT, with increased acute toxicity, but with comparable late toxicity. One trial, however, indicated increased late toxicity rates with UHRT.Discussion and conclusion: MHRT delivers similar therapeutic outcomes compared to CFRT in terms of tumour control and late toxicity for intermediate-risk PCa patients. Slightly more acute transient toxicity could be tolerated in favour of a shorter treatment course. UHRT should be regarded as an optional treatment for patients with low- and intermediate-risk disease applied at experienced centres in concordance with international and national guidelines.
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Malinda, Sella, Mega Iswari, and Jon Efendi. "Sebuah Adobe Flash CS6 dalam Menghitung Luas dan Keliling Bangun Datar Pada Anak Diskalkulia." Jurnal Pendidikan Kebutuhan Khusus 4, no. 1 (2020): 17. http://dx.doi.org/10.24036/jpkk.v4i1.50.
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Penelitian ini di latarbelakangi oleh permasalahan yang tampak di lapangan, yaitu anak diskalkulia di kelas V SDN 08 Surau Gadang Padang yang mengalami permasalahan dalam matematika mengenai materi menghitung luas dan keliling bangun datar. Penelitian ini menggunakan quasi experimental design dengan jenis one group pretest-posttest design. Hasil penelitian ini diperoleh berdasarkan analisis data yang dilihat dari skor pretest dan posttest. Data diolah menggunakan uji mann whitney. Diketahui n1 = 5 dan n2 = 5 pada taraf signifikan 95% dan α = 0,05 diperoleh Uhit = 0 dan Utab = 4. Hipotesis nol diterima karena Uhit ≤ Utab. Jadi, penggunaan media pembelajaran berbasis adobe flash CS6 tidak efektif dalam meningkatkan kemampuan menghitung luas dan keliling bangun datar pada anak diskalkulia di kelas V SDN 08 Surau Gadang Padang.
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Bartos, Stephen. "The Uhrig Report: Damp Squib or Ticking Timebomb?" Australian Journal of Public Administration 64, no. 1 (2005): 95–99. http://dx.doi.org/10.1111/j.1467-8500.2005.00421.x.
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Chubar, Oleg, Gianluca Geloni, Vitali Kocharyan, et al. "Ultra-high-resolution inelastic X-ray scattering at high-repetition-rate self-seeded X-ray free-electron lasers." Journal of Synchrotron Radiation 23, no. 2 (2016): 410–24. http://dx.doi.org/10.1107/s1600577515024844.
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Inelastic X-ray scattering (IXS) is an important tool for studies of equilibrium dynamics in condensed matter. A new spectrometer recently proposed for ultra-high-resolution IXS (UHRIX) has achieved 0.6 meV and 0.25 nm−1spectral and momentum-transfer resolutions, respectively. However, further improvements down to 0.1 meV and 0.02 nm−1are required to close the gap in energy–momentum space between high- and low-frequency probes. It is shown that this goal can be achieved by further optimizing the X-ray optics and by increasing the spectral flux of the incident X-ray pulses. UHRIX performs best at energies from 5 to 10 keV, where a combination of self-seeding and undulator tapering at the SASE-2 beamline of the European XFEL promises up to a 100-fold increase in average spectral flux compared with nominal SASE pulses at saturation, or three orders of magnitude more than what is possible with storage-ring-based radiation sources. Wave-optics calculations show that about 7 × 1012 photons s−1in a 90 µeV bandwidth can be achieved on the sample. This will provide unique new possibilities for dynamics studies by IXS.
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Irwanto, Fauzi, Mega Iswari, and Elsa Efrina. "Efektivitas Metode Maternal Reflektif dalam Meningkatkan Kemampuan Bahasa Anak Tunarungu." Jurnal Pendidikan Kebutuhan Khusus 2, no. 2 (2018): 25. http://dx.doi.org/10.24036/jpkk.v2i2.140.
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Penelitian ini dilatarbelakangi oleh permasalahan lima orang siswa tunarungu kelas VIII B di SLB Wacana Asih Padang yang mengalami masalah dalam bahasa ekspresif. Berdasarkan masalah diatas, penelitian ini bertujuan untuk membuktikan metode maternal reflektif dalam meningkatkan kemampuan mengucapkan kata bagi anak tunarungu kelas VIII di SLB Wacana Asih Padang. Jenis penelitian ini adalah quasi experiment dengan jenis one group pretest-posttest design. Subjek penelitian ini 5 orang siswa di SLB Wacana Asih Padang. Hasil penelitian ini menunjukkan, kemampuan anak dalam berbahasa ekspresif setelah dianalisis dengan melihat pesentase pada saat pretest yaitu 39% sedangkan untuk posttest terdapat peningkatan yakni menjadi 61%. Data diolah agar lebih ilmiah dengan menggunakan uji Mann Whitney. Diperoleh Uhit = 5 dan Utab = 2 dengan n = 5 pada taraf signifikan 95% dan α = 0,05. Hipotesis alternatif diterima karena Uhit > Utab, jadi disimpulkan bahwa metode maternal reflektif dapat meningkatkan kemampuan bahasa ekspresif pada anak tunarungu.
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Huotari, Vesa. "Tieteellisyys : kanto johtamiskoulutuksen kaskessa." Aikuiskasvatus 27, no. 3 (2007): 184–94. http://dx.doi.org/10.33336/aik.93764.
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”Tieteelliset työotteet ovat levittäytyneet yhä uusille toiminnan ja tekemisen alueille... Yksi niistä on johtamiskoulutus. Johtamiskoulutus onkin yksi tieteellisyyden uhri. Lupaus tieteelliselle tiedolle rakentuvasta, aikaisempaa vaikuttavammasta ja tehokkaammasta johtamisesta on ollut enemmän kuin mitä johtamistutkimus ja sille rakentuva yliopistollinen johtamiskoulutus on kyennyt kantamaan”, kirjoittaa Vesa Huotari artikkelissaan. Kirjoittaja jäsentää tieteellisen tutkimuksen ja yliopistollisen koulutuksen jännitteitä käyttäen viitekohtana kauppakorkeakoulujen antama MBA-koulutusta.
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Kuo, Wan-Jung, Gregory Quiroz, Gerardo Andres Paz-Silva, and Daniel A. Lidar. "Universality proof and analysis of generalized nested Uhrig dynamical decoupling." Journal of Mathematical Physics 53, no. 12 (2012): 122207. http://dx.doi.org/10.1063/1.4769382.
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Mönkkönen, Kaarina, Marja-Leena Hyvärinen, Taru Kekoni, Jenni Jaakkola, and Elisa Tiilikainen. "Moniammatillinen tiedonmuodostus - neuvottelua välitilassa." Janus Sosiaalipolitiikan ja sosiaalityön tutkimuksen aikakauslehti 30, no. 3 (2022): 232–50. http://dx.doi.org/10.30668/janus.115200.
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Tässä artikkelissa tutkimme lähisuhdeväkivaltaan kiinnittyvän simulaatioharjoituksen moniammatillista suunnitteluprosessia. Teoriaohjaavan tarkastelun kohteena on yhteisen tiedon muodostaminen, jota lähestymme liminaalitilan ja dialogisuuden käsitteillä ja toimintatutkimuksen lähtökohtia hyödyntäen. Tutkimusaineiston muodostavat moniammatilliseen simulaatioprosessiin osallistuneen suunnitteluryhmän yhteiset dokumentit, sähköpostiviestit, kirjalliset reflektoinnit sekä keskustelut, joita dokumentoitiin koko prosessin ajan. Aineisto analysointiin narratiivista analyysiä hyödyntäen. Analyysin tulokset osoittivat moniammatillisen tiedonmuodostuksen rakentuneen seuraavien yhteisten kysymysten ympärille: Kuka voi olla asiakas, Puheeksi ottaminen vai salassapito? ja Asetutaanko tukemaan uhria vai tekijää? Moniammatillisen suunnitteluprosessin lopputuloksena muodostui ammattilaisten kesken uusi jaettu näkemys, jossa näihin kysymyksiin liittyvät jännitteiset näkökulmat sovittuivat yhteen. Tutkimustulokset tuottavat uutta ymmärrystä siitä, miten tietoa voidaan rakentaa moniammatillisesti sensitiivisten kysymysten äärellä.
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Kaufmann, Wolfgang. "Max-Rainer Uhrig: Auf den Spuren des Phönix. Zur Kulturgeschichte der Feuerbestattung." Das Historisch-Politische Buch 67, no. 1 (2019): 119. http://dx.doi.org/10.3790/hpb.67.1.119a.
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Zulmiyetri, Zulmiyetri. "Efektivitas Media Gambar dapat Meningkatkan Mengenalkan Anggota Keluarga Inti bagi Anak Tunagrahita Sedang." Pedagogi: Jurnal Ilmu Pendidikan 12, no. 2 (2012): 58. http://dx.doi.org/10.24036/pedagogi.v12i2.2214.
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Tunagrahita child was a child with their ability is below average is between 51-36 compared with normal children her own age and kind of mental disorders, social emotional, speech and language, there are six (6) children tunagrahita being. This child have problems in speaking, this child would speak when it was forced by the teacher. Based on information from the teachers who are doing research on children mental retardation children have started to understand simple commands (receptive) for example, when the teacher said the child pray attitude immediately cupped his hands, his expression fixed on an object of interest, the ability of social interaction still need to be guided. The method uses a model quasi-experimental study used the experimental pretest-posttest control group, also known as one group pre-test post-test control group design with two kinds of treatment. The hypothesis of this study is: Ha image media are effective in improving core introduces family members of the child mental retardation were grade 1 in SLB 1 Padang. Ho: media images is not effective in improving core introduces family members of the child mental retardation were grade 1 in SLB 1 Padang. Testing hypotheses obtained with trials obtained Uhit U = 7.5 adjusted with tables on the significant level of 95% and a = 0.05 for n = 6 obtained Utab = 10. From the results obtained Uhit <Utab. This means that the Ha Ho rejected and accepted. Thus concluded that the level of a = 0.05 was not enough evidence to show a significant difference between the recognition ability of family members using the media images and without the use of media images mental retardation of the child being a class D 1 / C 1 in SLBN 1 Padang.
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Zulmiyetri, Zulmiyetri. "Efektivitas Media Gambar dapat Meningkatkan Mengenalkan Anggota Keluarga Inti bagi Anak Tunagrahita Sedang." Pedagogi: Jurnal Ilmu Pendidikan 12, no. 2 (2012): 58. http://dx.doi.org/10.24036/pendidikan.v12i2.2214.
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Tunagrahita child was a child with their ability is below average is between 51-36 compared with normal children her own age and kind of mental disorders, social emotional, speech and language, there are six (6) children tunagrahita being. This child have problems in speaking, this child would speak when it was forced by the teacher. Based on information from the teachers who are doing research on children mental retardation children have started to understand simple commands (receptive) for example, when the teacher said the child pray attitude immediately cupped his hands, his expression fixed on an object of interest, the ability of social interaction still need to be guided. The method uses a model quasi-experimental study used the experimental pretest-posttest control group, also known as one group pre-test post-test control group design with two kinds of treatment. The hypothesis of this study is: Ha image media are effective in improving core introduces family members of the child mental retardation were grade 1 in SLB 1 Padang. Ho: media images is not effective in improving core introduces family members of the child mental retardation were grade 1 in SLB 1 Padang. Testing hypotheses obtained with trials obtained Uhit U = 7.5 adjusted with tables on the significant level of 95% and a = 0.05 for n = 6 obtained Utab = 10. From the results obtained Uhit <Utab. This means that the Ha Ho rejected and accepted. Thus concluded that the level of a = 0.05 was not enough evidence to show a significant difference between the recognition ability of family members using the media images and without the use of media images mental retardation of the child being a class D 1 / C 1 in SLBN 1 Padang.
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Shu, Wenchong, Xinyu Zhao, Jun Jing, Lian-Ao Wu, and Ting Yu. "Uhrig dynamical control of a three-level system via non-Markovian quantum state diffusion." Journal of Physics B: Atomic, Molecular and Optical Physics 46, no. 17 (2013): 175504. http://dx.doi.org/10.1088/0953-4075/46/17/175504.
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CONG, SHUANG, LINPING CHAN, and JIANXIU LIU. "AN OPTIMIZED DYNAMICAL DECOUPLING STRATEGY TO SUPPRESS DECOHERENCE." International Journal of Quantum Information 09, no. 07n08 (2011): 1599–615. http://dx.doi.org/10.1142/s0219749911008428.
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In this paper, we first present a brief derivation of the dynamical decoupling condition by means of designing control Hamiltonians, which is used to preserve arbitrary quantum states in the case of interactions with environment. According to different time intervals between the adjacent pulses, two important dynamical decoupling schemes: periodic dynamical decoupling (PDD) and Uhrig dynamical decoupling (UDD) are analyzed. Based on the comparison between PDD and UDD, we propose our optimized dynamical decoupling scheme with different time intervals between adjacent pulses which follow a normal distribution. At last numerical simulations are carried out in a three-level atom in Ξ -configuration, we select the non-diagonal element of density matrix as a reference index to compare the performances of suppressing the decoherence of these three strategies, and the results indicate that dynamical decoupling strategy proposed has better performances than that of PDD and UDD have under some low range of the loss of the quantum coherence.
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Burgdorf, Wolfgang. "Uhrig, Hermann, Die Vereinbarkeit von Art. VII des Friedens von Lunéville mit der Reichsverfassung, 5 Bde." Zeitschrift der Savigny-Stiftung für Rechtsgeschichte: Germanistische Abteilung 134, no. 1 (2017): 523–25. http://dx.doi.org/10.26498/zrgga-2017-1340197.
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Skrine, Peter. "Changing Ideas, Changing Texts: First-Person Novels in the Early Modern Period by Reinhard Uhrig (review)." Modern Language Review 98, no. 4 (2003): 1076–77. http://dx.doi.org/10.1353/mlr.2003.a827435.
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Ghazi, Rabah Humam, Amsyaruddin Amsyaruddin, and Irdamurni Irdamurni. "Video Tutorial untuk Meningkatkan Keterampilan Memasang Kampas Rem bagi Anak Tunagrahita Ringan." Jurnal Pendidikan Kebutuhan Khusus 2, no. 1 (2018): 7. http://dx.doi.org/10.24036/jpkk.v2i1.29.
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The research was distributed by problems are five children of mild mental retardation class VII that have not been able to read the beginning with good and right so as to influence the outcome of learning they get. This research used an Agency Said method to form pre-experimental or quasy experiment with a kind of one group pretest-postest design. The research results show, a generation of kids able mental retardation in reading the beginning when analyzed by saw the value the average , when pre-test the child with mental retardation only 44 %. Next on posttest a generation of kids able mental retardation up by 78 % . Then the data processed that more scientific using the Mann Whitney test, obtained Uhit = 2.5 and Utab = 2 to the n = 5 the first significant 95 % and α = 0.05 .
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Siyanova-Chanturia, Anna. "Review of Herbst, Faulhaber & Uhrig (2011): The Phraseological View of Language. A Tribute to John Sinclair." International Journal of Corpus Linguistics 17, no. 4 (2012): 585–92. http://dx.doi.org/10.1075/ijcl.17.4.05siy.
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Oktafiani, Winda, Irdamurni Irdamurni, and Damri Damri. "EFEKTIVITAS MODEL PEMBELAJARAN COOPERATIVE INTEGRATED READING AND COMPOSITION (CIRC) UNTUK MENINGKATKAN KEMAMPUAN MEMBACA PEMAHAMAN ANAK DISLEKSIA." Unes Journal of Education Scienties 2, no. 1 (2018): 017. http://dx.doi.org/10.31933/ujes.2.1.017-022.2018.
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Penelitian ini dimotivasi oleh masalah yang ditemukan peneliti SDN 04 Garegeh Bukittinggi di kelas IV berjumlah lima siswa dengan ketidakmampuan belajar membaca pemahaman. Ini terbukti dari pengamatan yang peneliti lakukan, siswa tidak dapat memahami isi bacaan. Penelitian ini bertujuan untuk mengetahui sejauh mana keefektifan model pembelajaran kooperatif membaca dan komposisi kooperatif dalam meningkatkan kemampuan membaca pemahaman pada anak dengan ketidakmampuan belajar. Metode penelitian menggunakan pendekatan kuantitatif dengan desain penelitian adalah desain pra-eksperimental dengan one group pretest dan postest pre experiment. Teknik pengumpulan data yang digunakan adalah tes, dan alat pengumpulan data yang digunakan adalah teks wacana. Hasilnya dianalisis menggunakan uji Mann Whitney. Dengan kriteria tes penilaian ini adalah: hipotesis diterima jika Uhit> Utab pada tingkat signifikan 95% atau a = 0,05. Di luar kondisi ini hipotesis ditolak. Hasil penelitian menunjukkan bahwa rata-rata skor posttest siswa meningkat dari pretest setelah perawatan delapan kali. Kemampuan siswa untuk memahami membaca meningkat setelah mod CIRC belajar berlaku. Berdasarkan hasil penelitian ini disimpulkan bahwa model kooperatif membaca dan komposisi pembelajaran kooperatif secara efektif digunakan untuk meningkatkan pemahaman membaca pada anak dengan ketidakmampuan belajar.
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KIRKITADZE, Marina D., Colin HENDERSON, Nicholas C. PRICE, et al. "Central modules of the vaccinia virus complement control protein are not in extensive contact." Biochemical Journal 344, no. 1 (1999): 167–75. http://dx.doi.org/10.1042/bj3440167.
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The 28.6 kDa vaccinia virus complement control protein (VCP) is an inhibitor of the complement system and has therapeutic potential. It is composed of four domains or modules and is a homologue of complement receptor 1 (CR1) and other mammalian regulators of complement activation. A key aspect to structure-function relationships in these proteins is the extent of intramolecular module-module interactions, since these dictate the overall shape and flexibility of the molecules. A protein fragment (VCP∼ 2,3) encompassing modules 2 and 3 of VCP was over-expressed in Pichia pastoris. Ultracentrifugation showed that VCP∼ 2,3 is highly asymmetric with an axial ratio of 5.3:1, which is consistent with an end-to-end arrangement of the two modules. NMR spectroscopy, differential scanning calorimetry, CD and intrinsic tryptophan fluorescence were used to monitor unfolding of VCP∼ 2,3. Experiments performed over a range of temperatures and concentrations of guanidinium chloride revealed that module 2 unfolds under milder conditions than, and independently of, module 3. Unfolding of module 2 is not associated with extensive changes in amide 15N and 1H chemical shifts of module 3, implying that the modules do not form an extensive intermodular interface. Results obtained in this work for VCP∼ 2,3 are compared with those obtained in a study of CR1 modules 15-17 [Kirkitadze, Krych, Uhrin, Dryden, Smith, Cooper, Wang, Hauhart, Atkinson and Barlow (1999) Biochemistry 38, 7019-7031].
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Palander, Pälvi, Emma Brunberg, Camilla Munsterhjelm, Linda Keeling, Mari Heinonen, and Anna Valros. "Hännänpurentaan liittyvät sikojen väliset yksilölliset erot." Suomen Maataloustieteellisen Seuran Tiedote, no. 26 (January 31, 2010): 1–6. http://dx.doi.org/10.33354/smst.76876.
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Hännänpurenta on sikojen häiriökäyttäytymisen muoto, jonka tarkkaa alkuperää ei tunneta.Hännänpurennalle on kuitenkin löydetty laajoissa kartoituksissa lukuisia ympäristöperäisiäriskitekijöitä, jotka eivät kuitenkaan kaikilla yksilöillä johda hännänpurentakäyttäytymiseen.Yhteistä riskitekijöille on niiden aiheuttama stressi eläimelle. Sikayksilöt saattavat reagoidastressoreiden läsnäoloon yksilöllisesti, mikä selittäisi ilmiön, missä samassa ympäristössä yksisika puree ja toinen ei.Stressikäyttäytymistä voidaan tutkia vertaamalla stressiin liittyvien käyttäytymismuotojenesiintymistä ja aivoissa tapahtuvia neurobiologisia muutoksia ajallisesti ja määrällisesti.Serotoniini ja dopamiini ovat hermovälittäjäaineita, joilla on yhteys muun muassakäyttäytymiseen ja häiriökäyttäytymiseen. Kroonisen stressin tiedetään muuttavan aivojenrakennetta ja toimintaa.Tässä tutkimuksessa etsitään neurobiologisia ja fysiologisia eroja poikkeavasti janormaalisti käyttäytyvien sikayksilöiden välillä hännänpurennan aikana. Tutkittavat lihasiatjaettiin kolmeen ryhmään (PURIJA, UHRI, KONTROLLI) käyttäytymistarkkailun avulla saadunkeskimääräisen purentafrekvenssin mukaan. Ryhmiä verrataan anatomisten aivoalueiden(striatum, limbinen alue, etuaivokuori, hippokampus, talamus, hypotalamus) hermovälittäjäaineidenpitoisuuden ja niiden verenkierrossa olevien esiasteiden suhteen. Muita hännänpurentaan jastressiin liittyviä fysiologisia mekanismeja kartoitetaan määrittämällä kortisolin erityksenvuorokausirytmi syljestä, jejunumin alueen morfologinen suoliston kunto ja muu patologinen taihematologinen eroavuus ryhmien välillä. Tämä paperi keskittyy tutkimusten taustan jamenetelmien esittelyyn sekä koeryhmien identifiointiin. Fysiologisten näytteiden analysointi onyhä kesken.Tutkimus kuuluu yhteispohjoismaiseen NKJ- hankkeeseen “Tail biting and tail docking inthe pig: biological mechanisms, prevention, treatment and economic aspects”. Hankkeessaetsitään hännänpurentaan johtavia yksilöllisiä, ympäristö- ja rehuperäisiä riskitekijöitä, purentaaennaltaehkäiseviä ja purentaepidemian pysäyttäviä keinoja, toimivia hoidon- ja kivunlievityksenmuotoja ja mallitetaan hännänpurennan aiheuttamia taloudellisia kustannuksia.
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Al-Gaili, Mohammed Ali Hizam. "An Analysis of a New Musnad Inscription Related to Wars of Sabaʾ and dhū-Raydān Kings Found in Rayda City". Journal of Social Studies 25, № 2 (2019): 75–109. http://dx.doi.org/10.20428/jss.v25i2.1550.
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This research paper aimed to study the linguistic and historical connotations contained in the inscription (Al-Qayli-Rayda 1), which is an unpublished musnad inscription, representing a memorial text of the inscriptions of wars and military campaigns originating from the city of Rayda which is currently in the village of Bayt al-Qufāf, Ḫarif district, ʿAmrān, Yemen. To achieve this objective, the descriptive comparative analytical method was used. The analysis revealed that the events stated in the inscription date back to the era of the kings of Sabaʾ and dhū-Raydān (circa 3rd century AD). The inscriptions bnw S¹ʾrn w-Mḥylm indicate that there were a number of battles which can generally be divided into two campaigns. The first was launched by Rubʿ Rayda of Bakīl on the Bedouins, who had conquered ʿrn Baraṭ and some of the surrounding areas and valleys, and whose danger began to reach the eastern boundaries of Ḥas²id and Bakīl tribes. In the second campaign, the Rubʿ Rayda and other ʾArbāʿ of Bakīl under the command of a Kabīr Aqyānum and Ibn Marthadum, along with the king of Sabaʾ and dhū-Raydān (their names can be found in the left broken part of the inscription) launched the campaign, and headed to the S¹uhrat area to fight the ʾAshā‘ir tribe and its leader Nabat. The inscription is a new addition to Yemen's political history before Islam. It includes the areas on which the campaigns were launched and the methods and techniques used during the battles.
 Keywords: musnad inscription, Ridah city, war inscriptions, the era of Sheba and thi Ridan.
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Baldearamos, Germin, and María Elena Watson. "La pérdida lexical en la variante wanky en la ciudad de Bilwi: barrio “Filemón Rivera” y las comunidades de Uhri y Saklín, río Coco." Ciencia e Interculturalidad 3, no. 3 (2011): 57–65. http://dx.doi.org/10.5377/rci.v3i3.496.
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Las razones para la realización de este estudio se fundamentan en el deterioro y pérdida de la lengua miskitu, variante wanky, entre el grupo de hablantes dentro de la ciudad de Bilwi, Puerto Cabezas y comunidades del río Coco –Wangki Awala–, lo cual debe ser una preocupación para las autoridades gubernamentales de nuestra región y el país, profesionales en el área de educación, sociología y la cultura en general.El estudio es descriptivo, cualitativo y de corte longitudinal con el cual se permite identifcar los aspectos que han generado a la pérdida lexical de la lengua miskitu, para lo que se tomó en cuenta a la población del barrio “Filimon Rivera” (sector No. 3) y las comunidades de Uhri y Saklin en el municipio de Waspam, río Coco. En el presente estudio se realizaron entrevistas abiertas y observación participante, compartiendo con los hablantes en su lengua materna. Los resultados fueron los siguientes:Entre algunas de las palabras que están en desuso son: yamni, aisa, yapti, suapan, batanka, li klaswan, krukrutara, snik, pukrus, saurka. Sins watla, titan yamni, tutti yamni, tihmia yamni, yapti.Entre los elementos que afectan la pérdida lexical en la variante wanky se encuentran el mestizaje, la migración, los medio de comunicación radial, televisiva, emisoras quienes en un gran porcentaje emiten informaciones en la lengua que no es el miskitu y poco uso de la lengua miskitu ancestral en el hogar por parte de madres y padres de familia con sus hijas e hijos.
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Corrao, G., G. Marvaso, M. Pepa, et al. "PD-0575 UHRT for PCa with a DIL boost– a 5 year update with a focus on the impact of toxicity on QoL." Radiotherapy and Oncology 182 (May 2023): S456—S457. http://dx.doi.org/10.1016/s0167-8140(23)08925-9.
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Neukirch, Lasse, Patrick Schmidt, Inka Zörnig, Dirk Jäger, and Silke Uhrig-Schmidt. "Abstract 3563: CD8+ T cell-mediated tumor rejection by an Adeno-associated virus-like particle (AAVLP) vaccine." Cancer Research 82, no. 12_Supplement (2022): 3563. http://dx.doi.org/10.1158/1538-7445.am2022-3563.
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Abstract The utilization of adeno-associated viruses (AAVs) as vaccines has primarily been focused on the induction of antibody responses. Displaying antigens derived from HER2 or HPV on the AAV capsid surface lead to strong humoral immune responses. However, the potential of AAVs as T cell inducing vaccines has been poorly investigated. Model antigens have been inserted into the capsid of AAVs to analyze T cell responses, but these studies rather focused on preventing vector immunity for an improved tolerance of gene therapies. By using this as a starting point, we set out to test AAVs as T cell inducing vaccines with the prospect of targeting cancer neoantigens. In first experiments, the general properties of the vaccination strategy were estimated by displaying the ovalbumin-derived model antigen SIINFEKL on the surface of adeno-associated virus-like particles (AAVLPs). Upon injection of the AAVLP-SIINFEKL vaccine, mice developed strong CD8+ T cell responses against the displayed antigen. Highest immune responses were achieved by subcutaneous hock injection of AAVLPs, adjuvanted by Montanide ISA 51 VG. SIINFEKL-specific T cell responses peaked around three weeks after vaccination, whereas a memory subset remained present for long term. The anti-tumor efficacy of the vaccine was shown by injecting SIINFEKL-expressing B16F10 melanoma cells subcutaneously into mice, in which the tumor was completely rejected after vaccination. Interestingly, the induction of CD8+ T cell responses and the tumor protection depended on the presence of CD4+ T cells. Accordingly, T helper epitopes were identified in the AAVLP capsid sequence. In addition to the initial tests, a set of murine neoantigens, derived from B16F10 cells, were displayed on AAVLPs. In direct comparison to a peptide vaccine, which did not have an effect on tumor growth, the AAVLP vaccine had a significant impact on the tumor growth rate. In conclusion, AAVLPs show promising effects as T cell vaccines. The vaccination strategy can be used to induce cytotoxic T cell responses in general and anti-tumor effects in particular. AAV capsid-specific helper epitopes is one inherent advantage, since the AAVLP vaccine delivers immune stimulation within the viral particle itself. Thus, antigen-displaying AAVLPs could be an alternative to current gold standards in the field of neoantigen vaccines and have a prospect for future clinical applications. Citation Format: Lasse Neukirch, Patrick Schmidt, Inka Zörnig, Dirk Jäger, Silke Uhrig-Schmidt. CD8+ T cell-mediated tumor rejection by an Adeno-associated virus-like particle (AAVLP) vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3563.
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Louhela, Helena. "Tyttöjen toimijuus ja uhrius seksistisen väkivallan ja välittämisen kietoumassa." Nuorisotutkimus 41, no. 4 (2023): 58–70. http://dx.doi.org/10.57049/nuorisotutkimus.9142270.
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Tyttöihin ja naisiin kohdistuva seksistinen väkivalta on edelleen yksi maailman suurimmista ihmisoikeusrikkomuksista. Tyttöjen oma kokemus seksistisestä väkivallasta ei kuitenkaan aina ole linjassa vallitsevien normien kanssa. Tämän seurauksena tyttöjen mielipiteet ja tuntemukset väkivaltakokemuksistaan voivat tulla ohitetuiksi. Artikkelini kertoo siitä, kuinka nuori nainen sanallistaa ja tulkitsee fyysistä ja seksuaalista väkivaltaa sisältänyttä suhdettaan aikuisen miehen kanssa, joka lain mukaan määritellään lapsen seksuaalisena hyväksikäyttönä. Aineisto sisältää neljä 2010-luvun loppupuoliskolla toteutettua haastattelua haastateltavien ollessa 15–19-vuotiaita. Analyysissä hyödynnetään teoreettista viitekehystä, jonka kautta kuvaan, kuinka tyttöjen seksistisen väkivallan kokemuksiin voi nivoutua välittämisen tunteita sekä toimijuuden ja vaiennetuksi tulemisen ristiriitaista vaihtelua. Monenlaiset tekijät vaikuttavat siihen, millä tavoin tytöt suhtautuvat ja määrittelevät kokemansa seksistisen väkivallan. Tämän lisäksi yhteiskunnallinen normistomme asettaa tytöille ristiriitaisia odotuksia olla sekä aktiivinen toimija että oikeanlainen uhri väkivaltatilanteissa. Tutkimukseni haastaakin määrittelemään seksististä väkivaltailmiötä ja tyttöjen toimijuutta kontekstuaalisina ja tilannekohtaisina ilmiöinä. Tämän lähtökohdan kautta yhtenäistä terminologiaa tulisi kehittää nuorille ja kasvattajille seksistisen väkivallan ennaltaehkäisyyn ja jälkikäsittelyyn.
 Asiasanat: seksistinen väkivalta, toimijuus, tytöt, uhrius, välittäminen
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 Girls’ agency and victimization in the entanglement of sexist violence and caringHelena LouhelaThe Finnish Journal of Youth Research(Nuorisotutkimus) Vol 41 (4), 58–70
 Sexist violence against girls and women remains one of the biggest human rights violations in the world. Yet girls’ own experiences of sexist violence are not always in line with prevailing norms. As a result, girls’ opinions and feelings about their experiences of violence may be overlooked. This article explores how a young woman articulates and interprets her relationship with an adult man. The relationship involved physical and sexual violence, which is legally defined as child sexual abuse. The data includes four interviews conducted in the latter half of the 2010s when the interviewee was 15–19 years old. The analysis utilizes a theoretical reference framework to describe how feelings of caring and the contradictory alternation between agency and being silenced can be related to girls’ experiences of sexist violence.Many factors influence how girls relate to and define the sexist violence they experience. In addition, societal norms place conflicting expectations on girls to be both active agents and appropriate victims in violent situations. This research challenges the definition of the phenomenon of sexist violence and the agency of girls as a contextual and situational phenomenon. Based on this premise, a common terminology for the prevention and aftercare of sexist violence should be developed for young people and educators.
 Keywords: agency, caring, girls, sexist violence, victimization
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Shixian, Yan, Paul Schöpe, Joe Lewis, et al. "Abstract 2471: Novel Tetrazolo-pyridazine based MACC1 inhibitors are promising for anti-metastatic therapy." Cancer Research 83, no. 7_Supplement (2023): 2471. http://dx.doi.org/10.1158/1538-7445.am2023-2471.
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Abstract Cancer metastasis is the most lethal attribute of cancer, frequently caused by insufficient therapies and limited therapy options. Novel compounds able to interfere with metastasis formation are therefore of tremendous interest. Colorectal Cancer (CRC) is the third most prevalent and second most lethal cancer worldwide. In CRC, metastasis formation is linked to poor patient survival and treatment failure. Up to 90% of CRC related deaths are attributed to metastasis formation. Identification of causative drivers of metastasis represents the basis for effective anti-metastatic therapy. Our lab newly identified the gene MACC1 (Metastasis Associated in Colon Cancer 1). MACC1 is a key causal molecule for tumor progression and metastasis formation. It is a stage independent prognostic marker, predicting the onset of metastasis in stages I, II and III, based on tumor tissue analyses or blood-based tests. MACC1 promotes several cancer hallmark capabilities, providing cells with a malignant phenotype. Further, MACC1 has been established as a prognostic and predictive biomarker for metastasis in CRC and more than 20 other solid cancer entities. We therefore searched for novel compounds targeting MACC1 transcription. A high-throughput screen with more than 118,500 compounds (EMBL, Heidelberg), employing CRC cells stably transfected with a MACC1 promoter-luciferase reporter construct, revealed a Tetrazolo-pyridazine based compound as a promising lead for effective inhibition of MACC1 expression. We demonstrated that several SAR and MedChem-generated analogues of our lead compound effectively inhibit MACC1 gene expression and MACC1 driven cancer cell motility in vitro in CRC and cross entity cell lines. Further, they inhibit MACC1-induced tumor progression and metastasis in vivo in CRC xenograft models in mice. Moreover, ADMET studies were conducted, confirming our compounds are likely to be orally active drug with high stability in human plasma, low plasma protein binding and great permeability with neglectable efflux in MDR1-MDCKII assay. Through RNA-sequencing and subsequent gene set enrichment analysis a hypothesis on the mode of action was formed. An immune pathway has been identified as the most promising signaling pathway targeted by these compounds, which is currently explored through knock down and signaling studies. Taken together, this novel class of small molecules represents promising candidates for anti-metastatic therapy in CRC and other solid cancer patients in a personalized medicine setting. Citation Format: Yan Shixian, Paul Schöpe, Joe Lewis, Kerstin Putzker, Ulrike Uhrig, Edgar Specker, Jens von Kries, Hector E. Sanchez-Ibarra, Anke Unger, Mia Zischinsky, Bert Klebl, Peter Lindemann, Wolfgang Walther, Marc Nazaré, Dennis Kobelt, Ulrike Stein. Novel Tetrazolo-pyridazine based MACC1 inhibitors are promising for anti-metastatic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2471.
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Schöpe, Paul Curtis, Shixian Yan, Dennis Kobelt, et al. "Abstract A039: Novel tetrazolo-pyridazine based MACC1 transcriptional inhibitors as promising anti-metastatic therapy." Cancer Research 83, no. 2_Supplement_2 (2023): A039. http://dx.doi.org/10.1158/1538-7445.metastasis22-a039.
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Abstract The leading cause of cancer related deaths is the formation of metastasis, frequently caused by insufficient therapies and limited therapy options. Novel compounds able to interfere with metastasis formation are therefore of tremendous interest. Colorectal Cancer (CRC) is the third most prevalent and second most lethal cancer worldwide. In CRC, metastasis formation is linked to poor patient survival and treatment failure. Up to 90% of CRC related deaths are attributed to metastasis formation. Identification of causative drivers of metastasis represents the basis for effective anti-metastatic therapy. Our lab newly identified the gene MACC1 (Metastasis Associated in Colon Cancer 1) in 2009. Since then, MACC1 has been established as a key causal molecule for tumor progression and metastasis formation. It was shown that MACC1 can function as a stage independent prognostic marker, predicting the onset of metastasis in stages I, II and III, based on tumor tissue analyses or through a blood based test with an accuracy of up to 85%. MACC1 promotes several cancer hallmark capabilitites, providing cells with a malignant phenotype. Further, MACC1 has been established as a prognostic and predictive biomarker for metastasis in CRC and more than 20 other solid cancer entities. We therefore searched for novel compounds targeting MACC1 transcription. A high-throughput screen employing HCT116 cells stably transfected with a MACC1 promoter-luciferase reporter construct with more than 118,500 compounds was conducted at the EMBL in Heidelberg. The screen revealed a Tetrazolo-pyridazine based compound as a promising lead for effective inhibition of MACC1 expression. We demonstrated that several SAR and Medchem-generated analogues of our lead compound effectively inhibit MACC1 gene expression and MACC1 driven cancer cell motility in vitro in CRC and cross entity cell lines. Further, they inhibit MACC1-induced tumor progression and metastasis in vivo in a CRC xenograft model in mice. Moreover, ADMET studies were conducted, confirming our compounds are likely to be orally active drugs with high stability in human plasma, low plasma protein binding and great permeability with neglectable efflux in MDR1-MDCKII assay. Through RNA-sequencing and subsequent gene set enrichment analysis a first hypothesis on the mode of action was shaped. An immune pathway has been identified as the most promising signaling pathway targeted by these compounds and is currently explored through knock down and signaling studies. Taken together, this novel class of small molecules represents promising candidates for anti-metastatic therapy in CRC and other solid cancer patients in a personalized medicine setting. Funding: This study is adviced and financed by the SPARK BIH Program Citation Format: Paul Curtis Schöpe, Shixian Yan, Dennis Kobelt, Joe Lewis, Kerstin Putzker, Ulrike Uhrig, Edgar Specker, Jens Peter von Kries, Mathias Dahlmann, Hector E Sanchez-Ibarra, Anke Unger, Mia-Lisa Zischinsky, Bert Klebl, Peter Lindemann, Wolfgang Walther, Marc Nazaré, Ulrike Stein. Novel tetrazolo-pyridazine based MACC1 transcriptional inhibitors as promising anti-metastatic therapy [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A039.
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McBride, Sean Matthew, Daniel Eidelberg Spratt, Marisa Kollmeier, et al. "Interim results of aasur: A single arm, multi-center phase 2 trial of apalutamide (A) + abiraterone acetate + prednisone (AA+P) + leuprolide with stereotactic ultra-hypofractionated radiation (UHRT) in very high risk (VHR), node negative (N0) prostate cancer (PCa)." Journal of Clinical Oncology 39, no. 15_suppl (2021): 5012. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.5012.
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5012 Background: Standard of care in VHR PCa is radiation therapy (RT) with 18-36 months (mos) of androgen-deprivation therapy (ADT). With this regimen, chronic ADT toxicity is significant and biochemical recurrence (BCR) frequent. We sought to improve tumor control and minimize toxicity with intensified short course ADT with dual androgen receptor signaling inhibitors (ARSI) and UHRT. Methods: 64 patients (pts) with VHR, N0 PCa were enrolled from 4 centers. VHR PCa was defined as Gleason score (GS) 9-10, >4 cores of GS 8 disease, or 2 high-risk features (including rT3/T4 disease). Treatment (tx) involved 6 mos of A, AA+P, and leuprolide with prostate/seminal vesicle-directed RT (7.5-8 Gy x 5 fractions). The primary endpoint was BCR defined as nadir PSA + 2ng/mL. Biochemical recurrence-free survival (bRFS) is reported herein. Our hypothesized reduction in BCR from 25% to 10% at 3 years (yrs) required 53 pts to provide a power of 0.84 and an alpha of 0.03. Undetectable PSA was defined as <0.10 ng/mL. Non-castrate testosterone (T) was a post-tx value >150 ng/mL. All analyses were intention-to-treat. Toxicity and health-related quality of life measures were evaluated using CTCAEv4.0 and the EPIC-26 questionnaire. Results: Baseline characteristics are summarized in the Table; 63 of 64 pts completed protocol tx. Median time to nadir PSA from tx start was 2 mos (range, 1-9); 63 of 64 pts (98.4%) achieved an undetectable nadir PSA. Median time to post-tx, non-castrate T was 6.5 mos (range, 2.5-25.5). Median follow-up (f/u) for pts without BCR was 30 mos (range, 15-44). Seven pts had BCR; 2-yr bRFS was 95.0% (95% CI, 89.7-100); 3-yr bRFS was 89.7% (95 CI, 81.0-99.3). For the 57 pts without BCR, 56 (98.2%) had T > 150ng/mL at last f/u; median PSA at last f/u was 0.10 ng/mL (IQR, <0.10-0.30); of these, 40 (70.2%) pts had PSAs ≤ 0.20 ng/mL with 24 (42.1%) undetectable. Fifteen pts experienced transient Grade 3 toxicities: 12 (18.8%) with hypertension and 3 with rash (4.7%). EPIC-26 scores for a subset of pts (n=21) at baseline and 12 mos showed no significant decline in urinary or bowel domains; declines in sexual (-11.9) and hormone (-5.7) domains met significance. Conclusions: Compared to historic controls with the long course ADT, AASUR demonstrated impressive 3-yr bRFS, rapid T recovery, and limited toxicities; the safety profile of this regimen was consistent with the known AE profile of the ARSI and RT. This regimen warrants further, randomized evaluation. Funded by Janssen Pharmaceuticals. Managed by the Prostate Cancer Clinical Trials Consortium. Clinical trial information: NCT02772588. [Table: see text]
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Wurm, Alexander A., Silke Brilloff, Zunamys I. Carrero, et al. "Abstract 4110: Pathway activation driven miRNA depletion highlights cancer signaling vulnerabilities and targeted therapy sensitivity." Cancer Research 82, no. 12_Supplement (2022): 4110. http://dx.doi.org/10.1158/1538-7445.am2022-4110.
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Abstract Identification of cancer vulnerabilities is pivotal for the success of precision oncology. Comprehensive molecular profiling technologies improved clinical outcome of targeted drugs. However, the complexity of molecular interactions still challenges appropriate data interpretation. Hence, new strategies are needed to support current treatment decisions. One approach would be to consider additional molecular information, for instance microRNA (miRNA) expression patterns. By analyzing various cancer datasets, we observed that inhibition of miRNA expression occurs in a directed manner. Strong cancer driving mutations, such as in KRAS, result in a block of miRNAs inhibiting the cancer driver gene itself, or its associated downstream pathways. As many cancer drivers can activate diverse downstream pathways, we examined whether groups of strongly repressed miRNAs can uncover essential pathways. Therefore, we developed a miRNA depletion based cancer gene dependency model and related drug prediction workflow using miRNA sequencing data from cancer cell lines. We defined a pathway ranking score (PRS) and focused on druggable target genes. To validate our drug prediction workflow, we performed miRNA sequencing in various patient derived 3D cancer models (PDCMs). We predicted top hit pathway dependencies and individual druggable target genes for each culture. Subsequently, samples were used for in vitro drug response assays. Here, samples were significantly more sensitive to predicted targeted drugs, compared to standard of care (SOC) chemotherapy, or non-predicted targeted drugs. Next, we applied our miRNA based drug prediction workflow to four patients and compared three sources for RNA sequencing for each patient: PDCM, primary tumor, and microdissected purified tumor from FFPE tissue. Of note, FFPE purified miRNAs extraction led to comparable results to PDCMs and primary tumors. Finally, we were interested whether our prediction workflow matches with a comprehensive genomic based drug prediction workflow from the MASTER precision oncology trial. Therefore, we sequenced miRNAs from 95 patients and performed subsequent drug prediction. Interestingly, a complete overlap was overserved in only 20% of patients. In 35% of the patients, MASTER drug recommendation was biologically related to our drug prediction, and 40% revealed no match. In 75 out of 91 patients (82%) with available RNA Seq data, at least one of our predicted target genes was noticeably overexpressed on mRNA level. In total, 40% of all with our workflow predicted target genes, and 52% of druggable predicted target genes showed an increase of 1.5 fold or higher on RNA level compared to the entire cohort. In conclusion, unidirectional silenced miRNA expression signatures give further insights into cancer cell pathways and druggable gene dependencies and might be suitable tools for precision oncology. Citation Format: Alexander A. Wurm, Silke Brilloff, Zunamys I. Carrero, Stephan Drukewitz, Alexander Krüger, Sandra Oster, Sofia Kolovich, Melanie Hüther, Sebastian Uhrig, Dana Westphal, Friedegund Meier, Katrin Pfütze, Daniel Hübschmann, Peter Horak, Simon Kreutzfeldt, Christoph Heining, Daniela Richter, Stefan Fröhling, Claudia R. Ball, Hanno Glimm. Pathway activation driven miRNA depletion highlights cancer signaling vulnerabilities and targeted therapy sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4110.
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Schoepf, Julia, Sebastian Uhrig, Christoph E. Heilig, et al. "Abstract 4544: Genomic, transcriptomic, functional, and mechanistic characterization of rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusions." Cancer Research 83, no. 7_Supplement (2023): 4544. http://dx.doi.org/10.1158/1538-7445.am2023-4544.
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Abstract Rhabdomyosarcoma (RMS) is a soft-tissue sarcoma subtype composed of malignant immature precursor cells with myogenic differentiation defined by aberrant expression of the transcription factors MYOD1 and MYOG. Four subtypes are distinguished, characterized by considerable clinical, histologic, and genetic heterogeneity. RMS with fusions of the transcription factor TFCP2 to either FUS or EWSR1 has only recently been observed, but its classification and pathogenesis are unclear. We studied the clinical course, histopathology, and molecular landscape of 12 cases of this new RMS type and determined the functional properties of tumor-specific genetic alterations. Unusually for gene fusion-driven sarcomas, most tumors had highly rearranged genomes, including chromothripsis, and signs of defective homologous recombination DNA repair. All tumors were characterized by extremely high expression of a truncated TERT variant and the receptor tyrosine kinase ALK. The latter was additionally affected by intragenic deletions (33%), which resulted, together with aberrant splicing events, in the expression of shortened ALK variants (58%). Three ALK variants were oncogenic in immortalized cells in vitro and after xenotransplantation in mice and responded variably to different ALK inhibitors. Additional recurrent alterations included CDKN2A/MTAP co-deletions (67%) and mutations in PAPPA2 (25%) encoding an IGFBP5-specific proteinase. DNA methylation analysis of FUS/EWSR1-TFCP2 RMS, along with 19 other soft-tissue sarcoma types, revealed a close relationship with undifferentiated sarcoma but not with other RMS subtypes, suggesting that FUS/EWSR1-TFCP2 RMS is a distinct sarcoma entity possibly arising from a different cell of origin than other RMS types. Transduction of TFCP2 fusions into immortalized human cells conferred anchorage-independent growth and blocked late myogenic differentiation. Genes significantly induced in these cells were also highly expressed in patient tumors, including ALK, TERT, and two known regulators of skeletal muscle cells, IGFBP5 and PTH1R. ACT-seq demonstrated direct binding of FUS-TFCP2 to the ALK and TERT gene loci outside their regular promoters, which correlated with the expression of alternative transcript variants. Finally, FUS-TFCP2 appeared to induce a defect in DNA double-strand repair in immortalized cells, rendering them sensitive to treatment with cisplatin. Together, our study gives insights into the pathogenesis of a new RMS subtype defined by FUS-TFCP2 or EWSR1-TFCP2 fusions and suggests entry points for therapeutic intervention with DNA-damaging agents, ALK inhibitors, and, in the case of additional CDKN2A/MTAP co-deletion, drugs targeting PRMT5. Citation Format: Julia Schoepf, Sebastian Uhrig, Christoph E. Heilig, Kwang-Seok Lee, Tatjana Walther, Alexander Carazzato, Anna Maria Dobberkau, Dieter Weichenhan, Christoph Plass, Mark Hartmann, Gaurav Diwan, Zunamys Carrero, Claudia R. Ball, Tobias Hohl, Thomas Kindler, Patricia Rudolph-Hähnel, Anna Nilsson, Ingrid Øra, Roland Imle, Ana Banito, Robert Russell, Barbara C. Jones, Daniel B. Lipka, Hanno Glimm, Daniel Hübschmann, Wolfgang Hartmann, Stefan Fröhling, Claudia Scholl. Genomic, transcriptomic, functional, and mechanistic characterization of rhabdomyosarcoma with FUS-TFCP2 or EWSR1-TFCP2 fusions. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4544.
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Edwards, M. J. "‘Und das Wort ist Fleisch geworden’: Zur Rezeption von John 1,14a und zur Theologie der Fleischwerdung in der griechischen vornizänischen Patristik. By Christian Uhrig. Pp. 598. (Münsterische Beiträge zur Theologie, 63.) Münster: Aschendorff Verlag, 2004. isbn 3 402 03968 0. Paper €72." Journal of Theological Studies 57, no. 2 (2006): 709–11. http://dx.doi.org/10.1093/jts/fll001.
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Möhrmann, Lino, Lysann Rostock, Małgorzata Oleś, et al. "Abstract 926: Genomics-based personalized oncology of advanced thymic epithelial tumors." Cancer Research 83, no. 7_Supplement (2023): 926. http://dx.doi.org/10.1158/1538-7445.am2023-926.
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Abstract Introduction: Thymic epithelial tumors (TETs) are very rare. Thymoma A and AB have a better prognosis than more aggressive thymoma B, thymic carcinoma (TC) and neuroendocrine tumors of the thymus (NET). While previous efforts such as TCGA have mainly characterized thymomas (Radovich et al., Cancer Cell 2018), the molecular landscape of TCs and NETs is still elusive. Patients and Methods: Between 03/2014 and 07/2020, we enrolled 44 TET patients (27 TCs, 11 thymomas, 6 NETs) in a prospective observational study (MASTER) conducted by the National Center for Tumor Diseases (NCT) Heidelberg, NCT Dresden and the German Cancer Consortium (DKTK). MASTER applied whole genome/exome sequencing (WGS, n=22; WES, n=22), transcriptome (n=40) and germline analysis to inform therapy recommendations by a dedicated molecular tumor board (MTB). We systematically gathered follow-up data to evaluate outcome and compared progression-free survival (PFS) of the first treatment according to an MTB recommendation (PFS2) to the last prior systemic treatment (PFS1) in each patient (PFS ratio). Results: Tumor mutational burden (TMB) was low (median=0.99 mutations/Mb, range 0.08-3.48) but higher than in TCGA (p&lt;0.05). TMB was higher in TCs than in thymoma (p&lt;0.05). Most frequently mutated genes were TP53 (30%), CYLD (16%), SETD2 (14%) and KIT (14%). Germline analysis revealed (likely) pathogenic germline alterations in 25% of patients (MUTYH, n=3; BRCA1, n=2; BRCA2, BAP1, CHEK2, FANCA, TP53, MEN1, n=1). A comprehensive analysis of candidate biomarkers of homologous recombination repair (HRR) defects revealed a subgroup of TET patients with a rationale for PARP inhibitor therapy. Unsupervised clustering of RNA sequencing data mainly revealed clustering that correlated with WHO classification. Additionally, TCs clustered in two subgroups that we identified as immunologically hot and cold tumors using immunohistochemistry validation. Overall survival of patients with hot tumors was significantly longer (p&lt;0.05). The MTB recommended therapies for 42 patients (95%), which were implemented in 24 cases (57%). Five patients had a PFS2 &gt; 6 months and a PFS ratio &gt; 1.3. The best outcome was achieved using imatinib in a patient with a KIT mutation (p.W557R). After progression, the MTB recommended ponatinib based on a secondary KIT mutation (p.V654A). The patient was still on ponatinib when the observation period ended. Conclusion: We demonstrate that comprehensive molecular analysis provides clinically relevant information in a subgroup of TET patients. Thymoma, TCs, and NETs present with different molecular characteristics. Distinction between immunologically hot and cold TCs may have value for risk stratification and therapeutic strategies. PARP inhibition could be a potential new treatment option in a small subgroup of TETs. Molecular testing of KIT, germline analysis and genetic counseling should be recommended for all patients with advanced TETs. Citation Format: Lino Möhrmann, Lysann Rostock, Małgorzata Oleś, Arne Jahn, Marie Arlt, Nagarajan Paramasivam, Korinna Jöhrens, Luise Rupp, Marc Schmitz, Daniela Richter, Sebastian Uhrig, Martina Fröhlich, Barbara Hutter, Jennifer Hüllein, Elena E. Wolf, Dorothea Hanf, Laura Gieldon, Simon Kreutzfeldt, Christoph E. Heilig, Veronica Teleanu, Daniel B. Lipka, Andreas Mock, Ivan Jelas, Damian T. Rieke, Marcel Wiesweg, Melanie Boerries, Anna L. Illert, Alexander Desuki, Thomas Kindler, Angela M. Krackhardt, C. Benedikt Westphalen, Heidrun Grosch, Leonidas Apostolidis, Albrecht Stenzinger, Irina A. Kerle, Christoph Heining, Daniel Hübschmann, Evelin Schröck, Stefan Fröhling, Hanno Glimm. Genomics-based personalized oncology of advanced thymic epithelial tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 926.
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Kerbs, Paul, Aarif Mohamed Nazeer Batcha, Sebastian Vosberg, Dirk Metzler, Tobias Herold, and Philipp A. Greif. "Gene Fusion Detection By RNA-Seq in Acute Myeloid Leukemia (AML)." Blood 134, Supplement_1 (2019): 4655. http://dx.doi.org/10.1182/blood-2019-125869.
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Accurate and complete genetic classification of AML is crucial for the prediction of clinical outcome and treatment stratification. Deciphering the spectrum of genetic abnormalities by polymerase chain reaction (PCR), karyotyping and fluorescence in situ hybridization (FISH) in routine diagnostics is the current gold standard, however, fusion genes might potentially be missed by these assays. Recently, several methods have been developed to improve the detection of gene fusion transcripts based on RNA sequencing data, providing robust results. To test the detection power and assess the applicability of RNA-Seq based methods in clinical diagnostics we applied two different algorithms, namely FusionCatcher (Nicorici D et al., bioRxiv, 2014) and Arriba (Uhrig S et al., DKFZ, https://github.com/suhrig/arriba), to the transcriptomes of 895 well-characterized AML samples from three independently sequenced cohorts: AMLCG (Herold T et al., Haematologica, 2018, n=261), DKTK (Greif PA et al., Clin Cancer Res, 2018 and unpublished data, n=166), BeatAML (Tyner JW et al., Nature 2018, n=468) and publicly available healthy control samples (SRA studies: SRP018028, SRP047126, SRP050146, SRP105369, SRP115911, SRP133442, n=38). According to karyotyping, 31% (277/895) of samples harbored chromosomal aberrations putatively causing gene fusions (i.e. translocations, interstitial deletions, duplications, inversions, insertions). Analyses by FISH and/or PCR confirmed these rearrangements in 51.3% (142/277) of samples, whereas fusion detection by the means of RNA-Seq showed evidence for fusion genes corresponding to these rearrangements in 60.3% (167/277) of samples. Chromosomal aberrations, identified by karyotyping, which are known to result in clinically relevant fusions (e.g. RUNX1-RUNX1T1, KMT2A fusions) were confirmed by FISH/PCR (AMLCG: n=27/27, DKTK: n=21/21, BeatAML: n=54/57) and RNA-Seq based methods (AMLCG: n=17/27, DKTK: n=21/21, BeatAML: n=56/57) in most of the cases. Of note, the AMLCG cohort was sequenced using the SENSE mRNA Library Prep Kit from Lexogen which seems to be not optimal for fusion detection. Furthermore, 19 samples (AMLCG: n=12, DKTK: n=4, BeatAML: n=3) were found to harbor known pathogenic fusions, described in previous studies, which were not reported by routine diagnostics: NUP98-NSD1 (n=11); CBFB-MYH11, RUNX1-RUNX1T1 and DEK-NUP214 (n=2 each); RUNX1-CBFA2T2 and RUNX1-CBFA2T3 (n=1 each). Reanalysis of six of these samples by PCR confirmed three fusions which were initially missed by routine diagnostics. In general, the amount of reported fusion events by RNA-Seq is high (on average 69 and 39 per sample as detected by FusionCatcher and Arriba respectively), even after applying the built-in filters, indicating a high false positive rate. To robustly identify putative novel fusions, we developed a filtering pipeline and incorporated two new filtering steps. The promiscuity score (PS) of a fusion measures the amount of further distinct fusion partners which were detected in the respective cohort for the 5' and 3' gene. The fusion transcript score (FTS) measures the relative abundance of a fusion transcript to its 5' and 3' partner gene. PS and FTS of known, clinically relevant fusions confirmed by FISH/PCR were used to define cut-offs. To further maximize specificity while maintaining sensitivity, we excluded fusion events which we detected in publicly available healthy samples and subsequently filtered for overlapping calls from FusionCatcher and Arriba (Fig. 1A). Additionally, we obtained further evidence for a fusion event by an elevated transcription of the 3' fusion partner. In case of a fusion event, the transcription of the 3' partner gene likely gets under the control of the promoter of the 5' partner gene. This results in an elevated transcription of genes which are otherwise transcribed at low levels (Fig. 1B-C). Thus, we identified five putatively novel recurrent fusion genes which were detected in two cohorts independently: NRIP1-MIR99AHG, LATS2-ZMYM2, ATP11A-ING1, MBP-SLC66A2, PRDM16-SKI (Fig. 1D-F). Although these events were called with high evidence, we aim at independent validation by complementary methods. In our study, we have not only demonstrated that the application of RNA-Seq to the detection of fusion genes is a valuable complement to diagnostic routine but also has the potential to discover novel putatively pathogenic fusions. Disclosures No relevant conflicts of interest to declare.
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Jylhänkangas, Leila. "Ilona Kemppainen 2006: Isänmaan uhrit. Sankarikuolema Suomessa toisen maailmansodan aikana." Elore 13, no. 2 (2006). http://dx.doi.org/10.30666/elore.78605.
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Latina, Jacqueline M., Mahsima Shabani, Karan Kapoor, et al. "Abstract 15620: Diagnostic Performance of Ultra-high-resolution CT Coronary Angiography in Patients With Severe Coronary Artery Disease: Initial Experience." Circulation 142, Suppl_3 (2020). http://dx.doi.org/10.1161/circ.142.suppl_3.15620.
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Introduction: Conventional resolution coronary CTA (CRCT) is frequently avoided in patients with heavy calcification and prior stents given the diminished diagnostic accuracy. Ultra-high-resolution CT (UHRCT) with detector width of 0.25 mm may overcome partial volume effect limitations. Hypothesis: We hypothesize that UHRCT yields high accuracy for detecting obstructive coronary arterial stenoses in patients with severe coronary artery disease using cardiac catheterization as reference standard. Methods: Nine patients ≥45 years with severe coronary artery disease referred for invasive coronary angiography were prospectively enrolled at a single center. Patients underwent UHRCT within 30 days prior to catheterization and results for significant coronary artery stenoses (≥70%) by visual assessment by blinded expert readers for the two tests were compared. Diagnostic accuracy assessment was performed at a patient-level (N=9) and vessel-level (N=36). Results: Median patient age was 67 (range 53-77). Six patients were obese and 6 had prior stent placement. Estimated radiation dose was 9.3 mSv. Mean Agatston calcium score of patients without stents was 1,688. UHRCT correctly classified all patients as having obstructive or non-obstructive coronary heart disease, respectively, yielding 100% accuracy (95% confidence interval [CI] 64-100%). On a vessel level UHRCT had an accuracy of 93% (95% CI 78-98%). Conclusions: Our initial experience with UHRCT in patients with severe coronary calcification or prior stenting suggests high accuracy for detecting and excluding obstructive stenoses. These results warrant further studies to confirm a role of UHRCT in this challenging population.
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Han, Jae Sang, Dong-Hee Lee, Shi Nae Park, et al. "Evaluation of the reliability and validity of the upright head roll test for lateral semicircular canal benign paroxysmal positional vertigo." Journal of Vestibular Research, March 4, 2024, 1–10. http://dx.doi.org/10.3233/ves-230127.
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BACKGROUND: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV). OBJECTIVE: This study aimed to evaluate the reliability and validity of the UHRT. METHODS: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity. RESULTS: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen’s kappa = 0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen’s kappa = 0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0% ) and in differentiating the variant types (74.6% ). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen’s kappa = 0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen’s kappa = 0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (P < 0.05). CONCLUSION: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.
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Mishra, Rajnee, and Aurodeep Dasgupta. "Unilateral Heel-Raise Test: Estimating Normative Value and Reliability in Healthy Teenagers." Journal of Society of Indian Physiotherapists, July 22, 2024. http://dx.doi.org/10.4103/jsip.jsip_15_24.
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Abstract Background: The unilateral heel-raise test (UHRT) is a manual muscle testing procedure used to evaluate the power and endurance of the plantar flexors, which are important muscles for human locomotion. UHRT is commonly used in clinical practice, and normative reference values for UHRT in both adults and the pediatric population can be found in the literature. However, there is a lack of normative values for UHRT specifically for teenagers. The objective of this research study was to determine the normative value of UHRT and establish intra-and inter-tester reliability in teenagers in age group 13–17 years old. Materials and Methods: A total of 315 healthy adolescents were recruited as a part of this research. The participants were instructed to stand on the dominant foot by keeping the opposite foot off the ground (by flexing the knee to 90°). UHRT was performed actively up to maximum repetitions until the development of fatigue. Observations were recorded and further analyzed. Results: The inter- and intra-reliability of UHRT were ICC(2,k) = 0.83 (0.77–0.88) and ICC(3,1) = 0.83 (0.76–0.88), respectively. The median value (25th and 75th interquartile range) obtained for UHRT was 21 (18, 24). The Bland-Altman limits of agreement were also satisfied. The standard error of measurement (SEM) was 0.41, and the minimal detectable change (MDC) for the test was estimated to be 2. Conclusions: This study determined the normative values for UHRT in healthy teenagers of the age group 13–17 years old. It provides a valuable benchmark for interpreting the results of UHRT in teenagers. The analyses revealed good inter- and intra-reliability and minimal error, suggesting that it can be used objectively in research and clinical evaluations.
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Hoffmann, Thomas. "Speakers are creative, within limits — a response to Peter Uhrig." Cognitive Semiotics 13, no. 1 (2020). http://dx.doi.org/10.1515/cogsem-2020-2028.
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AbstractIn his contribution to the present volume, Uhrig (2020. Cognitive Semiotics 13, 1) focusses on an interesting question: When is a novel utterance considered “creative” and when is it seen as “wrong?” As I will show, Uhrig offers many important answers to this question. At the same time, I argue 1) that deliberateness is not (always) important for linguistic creativity; 2) that appropriateness requires a closer look; and 3) that frequency does not (always) play the most important role.
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Paukkonen, Nikolai. "Tukholman noitavainojen suomalainen uhri." Historiallinen Aikakauskirja 120, no. 1 (2022). http://dx.doi.org/10.54331/haik.131327.
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