BACKGROUNDCLN3 disease is a disorder of lysosomal homeostasis predominantly affecting the retina and the brain. The severity of the underlying mutations in CLN3 particularly determines onset and ...course of neurological deterioration. Given the highly conserved start codon code among eukaryotic species, we expected a variant in the start codon of CLN3 to give rise to the classical, that is, severe, phenotype. CASE SERIESWe present three patients with an identical CLN3 genotype (compound heterozygosity for the common 1 kb deletion in combination with a c.1A > C start codon variant) who all displayed a more attenuated phenotype than expected. While their retinal phenotype was similar to as expected in classical CLN3 disease, their neurological phenotype was delayed. Two patients had an early onset of cognitive impairment, but a particularly slow deterioration afterwards without any obvious motor impairment. The third patient also had a late onset of cognitive impairment. CONCLUSIONSContrasting our initial expectations, patients with a start codon variant in CLN3 may display a protracted phenotype. Future work will have to reveal the exact mechanism behind the assumed residual protein synthesis, and determine whether this may be eligible to start codon targeted therapy.
Background
: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and its incidence is rising. Diagnosis is mainly based on ultrasound performance whereas AFP measurement is not ...recommended according the current AASLD guidelines. The aim of this study is to determine the usefulness of α –fetoprotein (AFP), AFP-L3% and des-γ-carboxyprothrombin (DCP) in diagnosis of HCC and their correlation to clinicopathologic parameters.
Methods
: Both serum samples of 75 patients with confirmed HCC according the AASLD guidelines receiving transarterial chemoembolisation and of 175 patients with liver cirrhosis without evidence of HCC were prospectively collected. AFP, AFP–L3% and DCP were measured using a micro–total analysis system. Diagnostic accuracy was determined by ROC analysis reporting sensitivity, specificity and the area under the curve (AUC) with 95% confidence interval. Differences in marker values were calculated using non –parametric tests.
Results
: Optimal cut-off values for AFP, AFP – L3% and DCP were 10 ng/ml, 10% and 2.87 ng/ml with an AUC of 0.745, 0.784 and 0.777 respectively. Combination of all markers showed superior diagnostic accuracy with an AUC of 0.912 and yielded sensitivity and specificity of 93% (87% –99%) and 70% (63%–77%). Regarding patients with AFP < 20 ng/ml AFP-L3% showed sensitivity and specificity of 68% (54%–83%) and 89% (84%–94%) using 10% as the cut-off value. AFP, AFP – L3% and DCP were significantly higher in patients with multilocular HCC (p=0.008, p=0.004 and p=0.011 respectively). Moreover larger tumors and higher BCLC stage were associated with higher DCP values (p=0.042 and p=0.003).
Conclusions:
Combination of all markers showed a better diagnostic accuracy than using them alone. In patients with AFP < 20ng/ml AFP-L3% can be helpful in diagnosing HCC. DCP yielded a better association with clinicopathologic parameters than AFP and AFP-L3% and may provide further information concerning disease state.
Literatur:
1. Bruix J.Sherman M. (2011), Management of hepatocellular carcinoma: an update. Hepatology, 53: p. 1020-2. 2. Daniele B.,Bencivenga A.,Megna A.S.Tinessa V. (2004), Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology, 127: p. S108-12. 3. Gomaa A.I.,Khan S.A.,Leen E.L.,Waked I.Taylor-Robinson S.D. (2009), Diagnosis of hepatocellular carcinoma. World J Gastroenterol, 15: p. 1301-14. 4. Lee H.S.,Chung Y.H.Kim C.Y. (1991), Specificities of serum alpha-fetoprotein in HBsAg+ and HBsAg- patients in the diagnosis of hepatocellular carcinoma. Hepatology, 14: p. 68-72. 5. Namieno T.,Kawata A.,Sato N.,Kondo Y.Uchino J. (1995), Age-related, different clinicopathologic features of hepatocellular carcinoma patients. Ann Surg, 221: p. 308-14. 6. Tangkijvanich P.,Anukulkarnkusol N.,Suwangool P.,Lertmaharit S.,Hanvivatvong O.,KullavanijayaP.Poovorawan Y. (2000), Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol, 31: p. 302-8. 7. Shiraki K.,Takase K.,Tameda Y.,Hamada M.,Kosaka Y.Nakano T. (1995), A clinical study of lectin-reactive alpha-fetoprotein as an early indicator of hepatocellular carcinoma in the follow-up of cirrhotic patients. Hepatology, 22: p. 802-7. 8. Yamashita K.,Taketa K.,Nishi S.,Fukushima K.Ohkura T. (1993), Sugar chains of human cord serumalpha-fetoprotein: characteristics of N-linked sugar chains of glycoproteins produced in human liver and hepatocellular carcinomas. Cancer Res, 53: p. 2970-5. 9. Yoshima H.,Mizuochi T.,Ishii M.Kobata A. (1980), Structure of the asparagine-linked sugar chains of alpha-fetoprotein purified from human ascites fluid. Cancer Res, 40: p. 4276-81. 10. Khien V.V.,Mao H.V.,Chinh T.T.,Ha P.T.,Bang M.H.,Lac B.V.,Hop T.V.,Tuan N.A.,Don L.V.,Taketa K.Satomura S. (2001), Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology- proven hepatocellular carcinoma. Int J Biol Markers, 16: p. 105-11. 11. Oda K.,Ido A.,Tamai T.,Matsushita M.,Kumagai K.,Mawatari S.I.,Saishoji A.,Kure T.,Ohno K.,Toyokura E.,Imanaka D.,Moriuchi A.,Uto H.,Oketani M.,Hashiguchi T.Tsubouchi H. (2011), Highly sensitive lens culinaris agglutinin-reactive alpha-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease. Oncol Rep. 12. Carr B.I.,Kanke F.,Wise M.Satomura S. (2007), Clinical evaluation of lens culinaris agglutinin-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin in histologically proven hepatocellular carcinoma in the United States. Dig Dis Sci, 52: p. 776-82. 13. Nouso K.,Kobayashi Y.,Nakamura S.,Kobayashi S.,Takayama H.,Toshimori J.,Kuwaki K.,Hagihara H.,Onishi H.,Miyake Y.,Ikeda F.,Shiraha H.,Takaki A.,Iwasaki Y.,Kobashi H.Yamamoto K. (2011), Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein. J Gastroenterol Hepatol, 26: p. 1195-200. 14. Liebman H.A.,Furie B.C.,Tong M.J.,Blanchard R.A.,Lo K.J.,Lee S.D.,Coleman M.S.Furie B. (1984), Des- gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med, 310: p. 1427-31. 15. Shah D.V.,Engelke J.A.Suttie J.W. (1987), Abnormal prothrombin in the plasma of rats carrying hepatic tumors. Blood, 69: p. 850-4. 16. Shah D.V.,Zhang P.,Engelke J.A.,Bach A.U.Suttie J.W. (1993), Vitamin K-dependent carboxylase activity, prothrombin mRNA, and prothrombin production in two cultured rat hepatoma cell lines. Thromb Res, 70: p. 365-73. 17. Weitz I.C.Liebman H.A. (1993), Des-gamma-carboxy (abnormal) prothrombin and hepatocellular carcinoma: a critical review. Hepatology, 18: p. 990-7. 18. Yamaguchi I.,Nakamura K.,Kitano H.,Masuda Y.,Kanke F.,Kobatake S.Satomura S. (2008), Development of des-gamma-carboxy prothrombin (DCP) measuring reagent using the LiBASys clinical analyzer. Clin Chem Lab Med, 46: p. 411-6. 19. Ohhira M.,Saito H.,Suzuki Y.,Naraki T.,Sakurai S.,Ohtake T.,Suzuki M.,FujimotoKohgo Y. (2001), A variant of des-gamma-carboxy prothrombin was increased in alcoholic liver disease without hepatocellular carcinoma. Alcohol Clin Exp Res, 25: p. 46S-50S.
Astrophysical black holes could be nearly extremal (that is, rotating nearly as fast as possible); therefore, nearly extremal black holes could be among the binaries that current and future ...gravitational-wave observatories will detect. Predicting the gravitational waves emitted by merging black holes requires numerical-relativity simulations, but these simulations are especially challenging when one or both holes have mass \(m\) and spin \(S\) exceeding the Bowen-York limit of \(S/m^2=0.93\). We present improved methods that enable us to simulate merging, nearly extremal black holes more robustly and more efficiently. We use these methods to simulate an unequal-mass, precessing binary black hole coalescence, where the larger black hole has \(S/m^2=0.99\). We also use these methods to simulate a non-precessing binary black hole coalescence, where both black holes have \(S/m^2=0.994\), nearly reaching the Novikov-Thorne upper bound for holes spun up by thin accretion disks. We demonstrate numerical convergence and estimate the numerical errors of the waveforms; we compare numerical waveforms from our simulations with post-Newtonian and effective-one-body waveforms; we compare the evolution of the black-hole masses and spins with analytic predictions; and we explore the effect of increasing spin magnitude on the orbital dynamics (the so-called "orbital hangup" effect).
We demonstrate significant contributions of photovoltaic effects to the light-induced charge transport during hologram recording in BaTiO
3
:Fe. The photovoltaic effects are attributed to the motion ...of holes.
Context. The Sun is an active star that produces large-scale energetic events such as solar flares and coronal mass ejections and numerous smaller-scale events such as solar jets. These events are ...often associated with accelerated particles that can cause emission at radio wavelengths. The reconfiguration of the solar magnetic field in the corona is believed to be the cause of the majority of solar energetic events and accelerated particles. Aims. Here, we investigate a bright J-burst that was associated with a solar jet and the possible emission mechanism causing these two phenomena. Methods. We used data from the Solar Dynamics Observatory (SDO) to observe a solar jet, and radio data from the Low Frequency Array (LOFAR) and the Nançay Radioheliograph (NRH) to observe a J-burst over a broad frequency range (33-173 MHz) on 9 July 2013 at ~11:06 UT. Results. The J-burst showed fundamental and harmonic components and it was associated with a solar jet observed at extreme ultraviolet wavelengths with SDO. The solar jet occurred at a time and location coincident with the radio burst, in the northern hemisphere, and not inside a group of complex active regions in the southern hemisphere. The jet occurred in the negative polarity region of an area of bipolar plage. Newly emerged positive flux in this region appeared to be the trigger of the jet. Conclusions. Magnetic reconnection between the overlying coronal field lines and the newly emerged positive field lines is most likely the cause of the solar jet. Radio imaging provides a clear association between the jet and the J-burst which shows the path of the accelerated electrons.
A set of power supplies (PS) with output power rated from 100 W up to 10 kW for electromagnets powering was developed. These PS have range of current tuning of 60-80 db with high accuracy (error ...should be less than 0,01%). Some types of power supplies have bipolar output current. The report will describe a set of unified embedded devices for control and measurements of PS incorporated into distributed control systems. These embedded devices includes DAC, ADC with multiplexers and status Input/Output registers. The devices include microprocessor and allow work with minimal host involving. This capability decreases traffic, provides synchronous tuning of all electromagnet elements of particle accelerator and increases reliability of entire system.
Kryobiopsien sind ein mittlerweile in der Pulmologie etabliertes Verfahren, um einerseits ausreichend große Gewebspartikel bioptisch zu gewinnen für eine aussagekräftige histologische Aufarbeitung, ...andererseits wird dabei in aller Regel eine relativ nachblutungsarme Biopsie gewonnen (oft im Gegensatz zur konventionellen Zangenbiopsie). Darüber hinaus können mit der Kryo-Technik auch überraschend blutarme Rekanalisationen bei malignen Stenosen des oberen Atemwegstraktes vorgenommen werden.
Derzeit stehen sog. Kryosonden (Fa. Erbe, Tübingen) lediglich in kurzer Ausführung für Bronchoskope zur Verfügung; mit längeren, für Gastroskope geeigneten Sonden ist im Laufe des Jahres 2010 zu rechnen.
Anhand von 2 Fallbeispielen werden unsere ersten Erfahrungen mit der Kryobiopsie von gastrointestinalen Tumoren demonstriert (Leiomyosarkom des Ösophagus mit zuvor für die definitive Diagnosestellung nicht ausreichender Gewebsentnahme in der mehrfachen, auswärtig durchgeführten konventionellen Zangenbiopsie bzw. kontaktvulnerables Rektumkarzinom).
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