Background: To compare capecitabine/cisplatin with 5-fluorouracil/cisplatin as first-line treatment for advanced gastric cancer (AGC). Patients and methods: In this randomised, open-label, phase III ...study, patients received cisplatin (80 mg/m2 i.v. day 1) plus oral capecitabine (1000 mg/m2 b.i.d., days 1–14) (XP) or 5-FU (800 mg/m2/day by continuous infusion, days 1–5) (FP) every 3 weeks. The primary end point was to confirm noninferiority of XP versus FP for progression-free survival (PFS). Results: A total of 316 patients were randomised to XP (n = 160) or FP (n = 156). In the per-protocol population, median PFS for XP (n = 139) versus FP (n = 137) was 5.6 versus 5.0 months. The primary end point was met with an unadjusted hazard ratio (HR) of 0.81 95% confidence interval (CI) 0.63–1.04, P < 0.001 versus noninferiority margin of 1.25. Median overall survival was 10.5 versus 9.3 months for XP versus FP (unadjusted HR = 0.85, 95% CI 0.64–1.13, P = 0.008 versus noninferiority margin of 1.25). The most common treatment-related grade 3/4 adverse events in XP versus FP patients were as follows: neutropenia (16% versus 19%), vomiting (7% versus 8%), and stomatitis (2% versus 6%). Conclusions: XP showed significant noninferiority for PFS versus FP in the first-line treatment of AGC. XP can be considered an effective alternative to FP.
The aim of the study was to analyze the association between the superoxide dismutase 2 (SOD2) gene variants rs2758346, rs5746094, and rs2758331 and breast cancer (BC) in the Mexican population as ...well as to perform in silico assessments of the variants' potential impact.
We performed in silico analysis and analyzed 489 healthy women and 467 BC patients using TaqMan assays and Real-Time PCR.
The TT genotype, the T allele of the rs2758346 variant, and the CC genotype of both rs5746094 and rs2758331 were identified as BC risk factors (p < 0.05). The TT and CTTT genotype of the rs2758346 variant stratified by the presence of ki-67 (> 20%), TCCC, and estrogen receptor (ER)-positive of the rs5746094 variant, and the CC and CT genotypes of rs2758331 stratified by menopause status and non-chemotherapy response were risk factors. The TTC and TTA haplotypes are risk factors for BC. In silico analysis revealed that the rs2758346, rs5746094, and rs2758331 variants could influence SOD2 gene regulation by transcription factors and circulating RNAs (circRNAs).
The rs2758346, rs5746094, and rs2758331 variants of the SOD2 gene were associated with BC risk and could influence SOD2 regulation by transcription factors and circRNAs.
The 2001 classification subcommittee of the International League Against Epilepsy (ILAE) proposed to ‘group JME, juvenile absence epilepsy, and epilepsy with tonic clonic seizures only under the sole ...heading of idiopathic generalized epilepsies (IGE) with variable phenotype’. The implication is that juvenile myoclonic epilepsy (JME) does not exist as the sole phenotype of family members and that it should no longer be classified by itself or considered a distinct disease entity. Although recognized as a common form of epilepsy and presumed to be a lifelong trait, a long-term follow-up of JME has not been performed. To address these two issues, we studied 257 prospectively ascertained JME patients and encountered four groups: (i) classic JME (72%), (ii) CAE (childhood absence epilepsy) evolving to JME (18%), (iii) JME with adolescent absence (7%), and (iv) JME with astatic seizures (3%). We examined clinical and EEG phenotypes of family members and assessed clinical course over a mean of 11 ± 6 years and as long as 52 years. Forty per cent of JME families had JME as their sole clinical phenotype. Amongst relatives of classic JME families, JME was most common (40%) followed by grand mal (GM) only (35%). In contrast, 66% of families with CAE evolving to JME expressed the various phenotypes of IGE in family members. Absence seizures were more common in family members of CAE evolving to JME than in those of classic JME families (P < 0.001). Female preponderance, maternal transmission and poor response to treatment further characterized CAE evolving to JME. Only 7% of those with CAE evolving to JME were seizure-free compared with 58% of those with classic JME (P < 0.001), 56% with JME plus adolescent pyknoleptic absence and 62% with JME plus astatic seizures. Long-term follow-up (1–40 years for classic JME; 5–52 years for CAE evolving to JME, 5–26 years for JME with adolescent absence and 3–18 years for JME with astatic seizures) indicates that all subsyndromes are chronic and perhaps lifelong. Seven chromosome loci, three epilepsy-causing mutations and two genes with single nucleotide polymorphisms (SNPs) associating with JME reported in literature provide further evidence for JME as a distinct group of diseases.
To assess the usefulness of different imaging techniques in the detection of nodal involvement in patients with advanced cervical carcinoma. Moreover, to analyze the correlation between the ...presurgical (FIGO) and postsurgical (pTNM) staging classifications.
All patients diagnosed with advanced cervical cancer (FIGO Stages IIB-IV) from 2005 to 2012 were selected. The medical charts of 51 patients that underwent presurgical assessment with posterior surgical staging by means of para-aortic lymphadenectomy, were reviewed. Nodal status assessment by computed tomography scan (CT scan), magnetic resonance imaging (MRI), positron emission tomography (PET), and sonography was compared, as well as the size given in imaging techniques compared to the final pathologic report information.
Presurgical analysis by CT scan, MRI, PET, and sonography showed pelvic nodal involvement in 51.3% of patients, and para-aortic involvement in 30.8% of cases. CT scan showed positive pelvic nodes in 35% of cases, but pathologic confirmation was observed in just 17.6% of cases. However, MRI resulted in higher rates of up to 48.8% of cases. Concerning para-aortic nodal involvement, CT scan showed positive nodes in 25% of cases, MRI in 3.2% of cases, and the pathologic report in 15.6% of cases. The authors found significant differences between staging groups among both classifications (FIGO vs. pTNM; p < 0.001). Eight cases (15.7%) were understaged by FIGO classification.
Despite all imaging techniques available, none has demonstrated to be efficient enough to avoid the systematic study of para-aortic nodal status by means of surgical evaluation.
Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) concerning opinion on the evidence relating to dual antiplatelet therapy ...(DAPT) duration after coronary stenting.
Results from three randomised clinical trials were scheduled to be presented at the American Heart Association Scientific Sessions 2014 (AHA 2014). A web-based survey was distributed to all individuals registered in the EuroIntervention mailing list (n=15,200) both before and after AHA 2014. A total of 1,134 physicians responded to the first (i.e., before AHA 2014) and 542 to the second (i.e., after AHA 2014) survey. The majority of respondents interpreted trial results consistent with a substantial equipoise regarding the benefits and risks of an extended versus a standard DAPT strategy. Two respondents out of ten believed extended DAPT should be implemented in selected patients. After AHA 2014, 46.1% of participants expressed uncertainty about the available evidence on DAPT duration, and 40.0% the need for clinical guidance.
This EAPCI survey highlights considerable uncertainty within the medical community with regard to the optimal duration of DAPT after coronary stenting in the light of recent reported trial results. Updated recommendations for practising physicians to guide treatment decisions in routine clinical practice should be provided by international societies.
Web services work over dynamic connections among distributed systems. This technology was specifically designed to easily pass SOAP message through firewalls using open ports. These benefits involve ...a number of security challenges, such as Injection Attacks, phishing, Denial-of-Services (DoS) attacks, and so on. The difficulty to detect vulnerabilities,before they are exploited, encourages developers to use security testing like penetration testing to reduce the potential attacks. Given a black-box approach, this research use the penetration testing to emulate a series of attacks, such as Cross-site Scripting (XSS), Fuzzing Scan, Invalid Types, Malformed XML, SQL Injection, XPath Injection and XML Bomb. In this way, was used the soapUI vulnerability scanner in order to emulate these attacks and insert malicious scripts in the requests of the web services tested. Furthermore, was developed a set of rules to analyze the responses in order to reduce false positives and negatives. The results suggest that 97.1% of web services have at least one vulnerability of these attacks. We also determined a ranking of these attacks against web services.
Due to its distributed and open nature, Web Services give rise to new security challenges. This technology is susceptible to Cross-site Scripting (XSS) attack, which takes advantage of existing ...vulnerabilities. The proposed approach makes use of two Security Testing techniques, namely Penetration Testing and Fault Injection, in order to emulate XSS attack against Web Services. This technology, combined with WS-Security (WSS) and Security Tokens, can identify the sender and guarantee the legitimate access control to the SOAP messages exchanged. We use the vulnerability scanner soapUI that is one of the most recognized tools of Penetration Testing. In contrast, WSInject is a new fault injection tool, which introduces faults or errors on Web Services to analyze the behavior in an environment not robust. The results show that the use of WSInject, in comparison to soapUI, improves the detection of vulnerability allows to emulate XSS attack and generates new types of them.
A new version of the general circulation model CNRM-CM has been developed jointly by CNRM-GAME (Centre National de Recherches Météorologiques—Groupe d’études de l’Atmosphère Météorologique) and ...Cerfacs (Centre Européen de Recherche et de Formation Avancée) in order to contribute to phase 5 of the Coupled Model Intercomparison Project (CMIP5). The purpose of the study is to describe its main features and to provide a preliminary assessment of its mean climatology. CNRM-CM5.1 includes the atmospheric model ARPEGE-Climat (v5.2), the ocean model NEMO (v3.2), the land surface scheme ISBA and the sea ice model GELATO (v5) coupled through the OASIS (v3) system. The main improvements since CMIP3 are the following. Horizontal resolution has been increased both in the atmosphere (from 2.8° to 1.4°) and in the ocean (from 2° to 1°). The dynamical core of the atmospheric component has been revised. A new radiation scheme has been introduced and the treatments of tropospheric and stratospheric aerosols have been improved. Particular care has been devoted to ensure mass/water conservation in the atmospheric component. The land surface scheme ISBA has been externalised from the atmospheric model through the SURFEX platform and includes new developments such as a parameterization of sub-grid hydrology, a new freezing scheme and a new bulk parameterisation for ocean surface fluxes. The ocean model is based on the state-of-the-art version of NEMO, which has greatly progressed since the OPA8.0 version used in the CMIP3 version of CNRM-CM. Finally, the coupling between the different components through OASIS has also received a particular attention to avoid energy loss and spurious drifts. These developments generally lead to a more realistic representation of the mean recent climate and to a reduction of drifts in a preindustrial integration. The large-scale dynamics is generally improved both in the atmosphere and in the ocean, and the bias in mean surface temperature is clearly reduced. However, some flaws remain such as significant precipitation and radiative biases in many regions, or a pronounced drift in three dimensional salinity.
A
bstract
We present an updated global fit of neutrino oscillation data in the simplest three-neutrino framework. In the present study we include up-to-date analyses from a number of experiments. ...Concerning the atmospheric and solar sectors, besides the data considered previously, we give updated analyses of IceCube DeepCore and Sudbury Neutrino Observatory data, respectively. We have also included the latest electron antineutrino data collected by the Daya Bay and RENO reactor experiments, and the long-baseline T2K and NO
ν
A measurements, as reported in the Neutrino 2020 conference. All in all, these new analyses result in more accurate measurements of
θ
13
,
θ
12
,
Δ
m
21
2
and
Δ
m
31
2
. The best fit value for the atmospheric angle
θ
23
lies in the second octant, but first octant solutions remain allowed at ∼ 2
.
4
σ
. Regarding CP violation measurements, the preferred value of
δ
we obtain is 1.08
π
(1.58
π
) for normal (inverted) neutrino mass ordering. The global analysis still prefers normal neutrino mass ordering with 2.5
σ
statistical significance. This preference is milder than the one found in previous global analyses. These new results should be regarded as robust due to the agreement found between our Bayesian and frequentist approaches. Taking into account only oscillation data, there is a weak/moderate preference for the normal neutrino mass ordering of 2
.
00
σ
. While adding neutrinoless double beta decay from the latest Gerda, CUORE and KamLAND-Zen results barely modifies this picture, cosmological measurements raise the preference to 2
.
68
σ
within a conservative approach. A more aggressive data set combination of cosmological observations leads to a similar preference for normal with respect to inverted mass ordering, namely 2
.
70
σ
. This very same cosmological data set provides 2
σ
upper limits on the total neutrino mass corresponding to Σ
m
ν
<
0
.
12 (0
.
15) eV in the normal (inverted) neutrino mass ordering scenario. The bounds on the neutrino mixing parameters and masses presented in this up-to-date global fit analysis include all currently available neutrino physics inputs.
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