Fast simultaneous detection of K-RAS mutations in colorectal cancer

<p>Abstract</p> <p>Background</p> <p><it>RAS </it>genes acquire the most common somatic gain-of-function mutations in human cancer, and almost all of these mutations are located at codons 12, 13, 61, and 146.</p> <p>Methods</p> <p>We present a method for detecting these <it>K-RAS </it>hotspot mutations in 228 cases of colorectal cancer. The protocol is based on the multiplex amplification of exons 2, 3 and 4 in a single tube, followed by primer extension of the PCR products using various sizes of primers to detect base changes at codons 12, 13, 61 and 146. We compared the clinicopathological data of colorectal cancer patients with the <it>K-RAS </it>mutation status.</p> <p>Results</p> <p><it>K-RAS </it>mutation occurred in 36% (83/228) of our colorectal cancer cases. Univariate analysis revealed a significant association between <it>K-RAS </it>mutation at codon 12 of exon 2 and poor 5-year survival (p = 0.023) and lymph node involvement (p = 0.048). Also, <it>K-RAS </it>mutation at codon 13 of exon 2 correlates with the size of the tumor (p = 0.03). Multivariate analysis adjusted for tumor size, histologic grade, and lymph node metastasis also indicated <it>K-RAS </it>mutations at codon 12 and 13 of exon 2 correlate significantly with overall survival (p = 0.002 and 0.025). No association was observed between codon 61 and 146 and clinicopathological features.</p> <p>Conclusion</p> <p>We demonstrated a simple and fast way to identify <it>K-RAS </it>mutation.</p

Categorizing Different Approaches to the Cosmological Constant Problem

We have found that proposals addressing the old cosmological constant problem come in various categories. The aim of this paper is to identify as many different, credible mechanisms as possible and to provide them with a code for future reference. We find that they all can be classified into five different schemes of which we indicate the advantages and drawbacks. Besides, we add a new approach based on a symmetry principle mapping real to imaginary spacetime.Comment: updated version, accepted for publicatio

Effect of wind speed on aerosol optical depth over remote oceans, based on data from the Maritime Aerosol Network

The Maritime Aerosol Network (MAN) has been collecting data over the oceans since November 2006. The MAN archive provides a valuable resource for aerosol studies in maritime environments. In the current paper we investigate correlations between ship-borne aerosol optical depth (AOD) and near-surface wind speed, either measured (onboard or from satellite) or modeled (NCEP). According to our analysis, wind speed influences columnar aerosol optical depth, although the slope of the linear regression between AOD and wind speed is not steep (~0.004–0.005), even for strong winds over 10 m s−1. The relationships show significant scatter (correlation coefficients typically in the range 0.3–0.5); the majority of this scatter can be explained by the uncertainty on the input data. The various wind speed sources considered yield similar patterns. Results are in good agreement with the majority of previously published relationships between surface wind speed and ship-based or satellite-based AOD measurements. The basic relationships are similar for all the wind speed sources considered; however, the gradient of the relationship varies by around a factor of two depending on the wind data used

Angioplasty versus stenting for infrapopliteal arterial lesions in chronic limb-threatening ischaemia

Background: Chronic limb-threatening ischaemia (CLTI) is a manifestation of peripheral arterial disease (PAD) that includes chronic ischaemic rest pain or ischaemic skin lesions, ulcers, or gangrene for longer than two weeks. The severity of the disease depends on the extent of arterial stenosis and the availability of collateral circulation. Treatment for CLTI aims to relieve ischaemic pain, heal ischaemic ulcers, prevent limb loss, improve quality of life, and prolong survival. CLTI due to occlusive disease in the infrapopliteal arterial circulation (below-knee circulation) can be treated via an endovascular technique by a balloon opening the narrowed vessel, so called angioplasty, with or without the additional deployment of a scaffold made of metal alloy or other material, so called stenting. Endovascular interventions in the infrapopliteal vasculature may improve symptoms in patients with CLTI by re-establishing in-line blood flow to the foot. Controversy remains as to whether a balloon should be used alone to open the vessel, or whether a stent should also be deployed. Objectives: To determine the efficacy and safety of percutaneous transluminal angioplasty (PTA) alone versus PTA with stenting of infrapopliteal arterial lesions (anterior tibial artery, posterior tibial artery, fibular artery (formerly known as peroneal artery), and common tibioperoneal trunk) for patients with chronic limb-threatening ischaemia (CLTI). Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, as well as World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 25 June 2018. We applied no language restrictions. Selection criteria: We planned to include randomised or quasi-randomised controlled trials comparing PTA versus PTA with a stent and including patients aged 18 years or over with CLTI. We defined CLTI as Fontaine stage III (ischaemic rest pain) and IV (ischaemic ulcers or gangrene) or consistent with Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss), and 6 (major tissue loss), with stenotic (> 50% luminal loss) or occluded infrapopliteal artery, including tibiofibular trunk, anterior tibial artery, posterior tibial artery, and fibular artery. We included all types of stents irrespective of design (e.g. bare-metal, drug-eluting, bio-absorbable). Data collection and analysis: Two review authors (CC-TH and GNCK) independently selected suitable trials, assessed trial quality, and extracted data. An additional third review author (MLvD) assessed trial quality and, when necessary, acted as arbiter for study selection and data extraction. Outcomes included technical success of the procedure, procedural complications, patency, major amputation, and mortality. We assessed the quality of evidence using the GRADE approach. Main results: We included in the review seven trials with 542 participants. One trial randomised limbs to undergo PTA alone or PTA with stent placement, and the remaining studies randomised participants. Five trials with 476 participants show that the technical success rate was greater in the stent group than in the angioplasty group (odds ratio (OR) 3.00, 95% confidence interval (CI) 1.14 to 7.93; 476 lesions; 5 studies; I2 = 23%). Meta-analysis of three eligible trials with 456 participants did not show a clear difference in short-term (within six months) patency between infrapopliteal arterial lesions treated with PTA and those treated with PTA and stenting (OR 0.88, 95% CI 0.37 to 2.11; 456 lesions; 3 studies; I2 = 77%). Results also did not show clear differences between treatment groups in procedure complication rate (OR 0.87, 95% CI 0.01 to 53.60; 360 participants; 5 studies; I2 = 85%), rate of major amputations at 12 months (OR 1.34, 95% CI 0.56 to 3.22; 306 participants; 4 studies; I2 = 0%), and rate of mortality at 12 months (OR 0.71, 95% CI 0.43 to 1.17; 497 participants; 6 studies; I2 = 0%). Heterogeneity between studies was high for the outcomes procedure complications and primary patency. The overall methodological quality of the trials included in this review was moderate due to selection and performance bias. Studies used different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication. We downgraded the certainty of the overall evidence for all outcomes by one level to moderate due to inconsistency of results across studies and large confidence intervals (small numbers of trials and participants). Authors' conclusions: Trials show that the immediate technical success rate of restoring luminal patency is higher in the stent group but reveal no clear differences in short-term patency at six months between infrapopliteal arterial lesions treated with PTA with stenting versus those treated with PTA without stenting. We ascertained no clear differences between groups in periprocedural complications, major amputation, and mortality. However, use of different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication and the duration of its use within and between trials may have influenced the outcomes. Limited currently available data suggest that high-quality evidence is insufficient to show that PTA with stent insertion is superior to use of standard PTA alone without stenting for treatment of infrapopliteal arterial lesions. Further studies should standardise the use of antiplatelets/anticoagulants before and after the intervention to improve the comparability of the two treatments

HUBUNGAN DUKUNGAN KELUARGA DENGAN TINGKAT DEPRESI PADA NARAPIDANA NAPZA DI RUTAN KELAS IIB KAJHU ACEH BESAR

Banda Ace

Measurement of the Branching Fraction for B->eta' K and Search for B->eta'pi+

We report measurements for two-body charmless B decays with an eta' meson in the final state. Using 11.1X10^6 BBbar pairs collected with the Belle detector, we find BF(B^+ ->eta'K^+)=(79^+12_-11 +-9)x10^-6 and BF(B^0 -> eta'K^0)=(55^+19_-16 +-8)x10^-6, where the first and second errors are statistical and systematic, respectively. No signal is observed in the mode B^+ -> eta' pi^+, and we set a 90% confidence level upper limit of BF(B^+-> eta'pi^+) eta'K^+- decays is investigated and a limit at 90% confidence level of -0.20<Acp<0.32 is obtained.Comment: Submitted to Physics Letters

Observation of Cabibbo-suppressed and W-exchange Lambda_c^+ baryon decays

We present measurements of the Cabibbo-suppressed decays Lambda_c^+ --> Lambda0 K+ and Lambda_c^+ --> Sigma0 K+ (both first observations), Lambda_c^+ --> Sigma+ K+ pi- (seen with large statistics for the first time), Lambda_c^+ --> p K+ K- and Lambda_c^+ --> p phi (measured with improved accuracy). Improved branching ratio measurements for the decays Lambda_c^+ --> Sigma+ K+ K- and Lambda_c^+ --> Sigma+ phi, which are attributed to W-exchange diagrams, are shown. We also present the first evidence for Lambda_c^+ --> Xi(1690)^0 K+ and set an upper limit on the non-resonant decay Lambda_c^+ --> Sigma+ K+ K-. This analysis was performed using 32.6 fb^{-1} of data collected by the Belle detector at the asymmetric e+ e- collider KEKB.Comment: Submitted to Phys. Lett. B. v2: A small correction to the Authorlist was made. An earlier version of this analysis was released as BELLE-CONF-0130, hep-ex/010800

Measurement of the inclusive semileptonic branching fraction of B mesons and |Vcb|

We present a measurement of the electron spectrum from inclusive semileptonic {\it B} decay, using 5.1 fb$^{-1}$ of $\Upsilon(4S)$ data collected with the Belle detector. A high-momentum lepton tag was used to separate the semileptonic {\it B} decay electrons from secondary decay electrons. We obtained the branching fraction, ${\cal B}(B\to X e^+ \nu) = (10.90 \pm 0.12 \pm 0.49)$, with minimal model dependence. From this measurement, we derive a value for the Cabibbo-Kobayashi-Maskawa matrix element $|V_{cb}| = 0.0408 \pm 0.0010 {\rm (exp)} \pm 0.0025{\rm (th)}$.Comment: 16 pages, 3 figures, 3 table

Determination of |Vcb| using the semileptonic decay \bar{B}^0 --> D^{*+}e^-\bar{\nu}

We present a measurement of the Cabibbo-Kobayashi-Maskawa (CKM) matrix element |Vcb| using a 10.2 fb^{-1} data sample recorded at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e^+e^- storage ring. By extrapolating the differential decay width of the \bar{B}^0 --> D^{*+}e^-\bar{\nu} decay to the kinematic limit at which the D^{*+} is at rest with respect to the \bar{B}^0, we extract the product of |Vcb| with the normalization of the decay form factor F(1), |Vcb |F(1)= (3.54+/-0.19+/-0.18)x10^{-2}, where the first error is statistical and the second is systematic. A value of |Vcb| = (3.88+/-0.21+/-0.20+/-0.19)x10^{-2} is obtained using a theoretical calculation of F(1), where the third error is due to the theoretical uncertainty in the value of F(1). The branching fraction B(\bar{B}^0 --> D^{*+}e^-\bar{\nu}) is measured to be (4.59+/-0.23+/-0.40)x10^{-2}.Comment: 20 pages, 6 figures, elsart.cls, submitted to PL

A Measurement of the Branching Fraction for the Inclusive B --> X(s) gamma Decays with the Belle Detector

We have measured the branching fraction of the inclusive radiative B meson decay B --> X(s) gamma to be Br(B->X(s)gamma)=(3.36 +/- 0.53(stat) +/- 0.42(sys) +0.50-0.54(th)) x 10^{-4}. The result is based on a sample of 6.07 x 10^6 BBbar events collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e^+e^- storage ring.Comment: 14 pages, 6 Postsript figures, uses elsart.cl