373 research outputs found
Evolution of monogenetic rhyolite volcanoes: Vinicky, Eastern Slovakia
Four essential volcanic units have been recognized
in the late Middle Miocene rhyolite complex at
the southern side of the ZemplĂn horst next to the
village ViniÄŤky. A succession of ash/pumice flow,
surge and fall deposits separated by horizons of
eolian dust and paleosoil in total thickness >15
m forms the lower unit. It represents distal facies
deposits of subplinian/plinian/phreatoplinian type
eruptions at unidentified centers. The second
unit rests upon the lower one with unconformity
marking a
period of erosion.
It
consists of coarse
phreatic/phreatomagmatic pyroclastic rocks with
fragments of basement rocks and glassy dacite/
rhyodacite. They represent proximal facies of a
phreatomagmatic pyroclastic ring. Both units are
truncated by a rhyolite extrusive dome, formed
of perlite and perlitic breccias at its margin.
Emplacement of the dome concluded activity of
local centers northwest of ViniÄŤky. An extensive
rhyolite coulee represents the fourth, uppermost
volcanic unit. It is 40 – 70 m thick, formed of
felsitic rhyolite with perlite and perlitic breccia
at the base. Orientation of flow banding implies
that the Borsuk extrusive dome 1
km northeast
of ViniÄŤky was a source of the coulee. The dome
and coulee form together one rhyolite body of the
dome-flow type. With exception of the distal facies
tuffs at the base the rhyolite complex represents
most probably products of three overlapping
monogenetic volcanoe
Complex gunshot injury to the heart as a consequence of suicide attempt in a schizophrenic patient
AbstractIntroductionSelf-inflicted gunshot injury to the heart is uncommon in Western Europe countries. However it is considered to have a high mortality through cardiac tamponade or exsanguination and concomitant chest or abdominal cavity injury.Case presentationWe present a 39-year-old schizophrenic woman who attempted suicide with the aid of a 6.35mm caliber handgun, after self-discontinuing of antipsychotic treatment. Lower third of sternum, right heart atrium and ventricle and inferior caval vein were hit by the bullet which consequently got lodged in the right paravertebral muscle mass at the lower thoracic vertebral level. As she was hemodynamically unstable due to hemopericardium and a huge right hemothorax, she underwent emergent surgery. Heart and inferior vena caval injuries were repaired on extracorporeal circulation. The postoperative course was uneventful and she was transferred to a psychiatric facility on the 7th postoperative day. One year after the surgery she is well, compliant to antipsychotic medications and on periodic follow-up by psychiatrists.ConclusionThis case represents management of complex self-inflicted gunshot cardiac injury in a schizophrenic patient who discontinued antipsychotic medication. Liaison between themedical rescue service and high level trauma center essentially reduced injury-to-surgery time. Complex heart injury was successfully repaired on extracorporeal circulation
Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2
Objective:
An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC).
Methods:
Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments.
Results:
In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred.
Conclusions:
Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile
Radio-Frequency Measurements of Coherent Transition and Cherenkov Radiation: Implications for High-Energy Neutrino Detection
We report on measurements of 11-18 cm wavelength radio emission from
interactions of 15.2 MeV pulsed electron bunches at the Argonne Wakefield
Accelerator. The electrons were observed both in a configuration where they
produced primarily transition radiation from an aluminum foil, and in a
configuration designed for the electrons to produce Cherenkov radiation in a
silica sand target. Our aim was to emulate the large electron excess expected
to develop during an electromagnetic cascade initiated by an ultra high-energy
particle. Such charge asymmetries are predicted to produce strong coherent
radio pulses, which are the basis for several experiments to detect high-energy
neutrinos from the showers they induce in Antarctic ice and in the lunar
regolith. We detected coherent emission which we attribute both to transition
and possibly Cherenkov radiation at different levels depending on the
experimental conditions. We discuss implications for experiments relying on
radio emission for detection of electromagnetic cascades produced by ultra
high-energy neutrinos.Comment: updated figure 10; fixed typo in equation 2.2; accepted by PR
Impact of Local Congruences in Attribute Reduction
Local congruences are equivalence relations whose equivalence classes are convex sublattices of the original lattice. In this paper,
we present a study that relates local congruences to attribute reduction
in FCA. Specifically, we will analyze the impact in the context of the use
of local congruences, when they are used for complementing an attribute
reduction
ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer
PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells
In this study, we explore the therapeutic potential of lapatinib a selective inhibitor of both the EGFR and HER2 tyrosine kinases for the treatment of endometrial cancer. The effect of lapatinib on tumour cell growth and receptor activation was studied in a panel of human endometrial cancer cell lines. Candidate molecular markers predicting sensitivity were assessed by baseline gene expression profiling, ELISA, and western blot analyses. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions between chemotherapeutic drugs and lapatinib. Concentration-dependent anti-proliferative effects of lapatinib were seen in all endometrial cancer cell lines tested, but varied significantly between individual cell lines (IC50 range: 0.052–10.9 μmol). HER2 overexpression or increased expression of EGFR was significantly associated with in vitro sensitivity (P=0.024 or 0.011, respectively). Lapatinib exerts growth inhibition in a PTEN-independent manner. Sensitive cell lines also exhibited increased expression of EGFR ligands or HER3. In contrast, lapatinib-resistant cell lines exhibited high androgen receptor (AR) levels or epithelial-to-mesenchymal transition (post-EMT) features. In endometrial cancer cells, at a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for lapatinib plus carboplatin, paclitaxel, docetaxel, and doxorubicin. These observations provide a clear biologic rational to test lapatinib as a single agent or in combination with chemotherapy in endometrial cancer with HER2 overexpression. Expression of EGFR, its ligands, HER3, AR, and post-EMT markers warrant further evaluation to help define patients with HER2-nonoverexpressing endometrial cancer most likely to benefit from lapatinib
High power testing of a fused quartz-based dielectricloaded accelerating structure
We report on the most recent results from a series of high power tests being carried out on rf-driven dielectric loaded accelerating (DLA) structures. The purpose of these tests is to determine the viability of the DLA as a traveling-wave accelerator and is a collaborative effort between Argonne National Laboratory (ANL), Naval Research Laboratory (NRL), and Stanford Linear Accelerator Center (SLAC). In this paper, we report on the recent high power tests of a fused quartz-based DLA structure that was carried out at incident powers of up to 12 MW at NRL and 37 MW at SLAC. We also report on test results of a TiN coated quartz structure, that exhibits good multipactor suppression
HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer
Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial.
Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro.
Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors.
Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group
- …