Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

<p>Abstract</p> <p>Background</p> <p>Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.</p> <p>Methods</p> <p>Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.</p> <p>Results</p> <p>1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).</p> <p>Conclusions</p> <p>Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.</p> <p>Trial Registration</p> <p>clinicaltrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00451412">NCT00451412</a></p

Direct Evidence of Two-component Ejecta in Supernova 2016gkg from Nebular Spectroscopy*

Spectral observations of the type-IIb supernova (SN) 2016gkg at 300-800 days are reported. The spectra show nebular characteristics, revealing emission from the progenitor star's metal-rich core and providing clues to the kinematics and physical conditions of the explosion. The nebular spectra are dominated by emission lines of [O i] lambda lambda 6300, 6364 and [Ca ii] lambda lambda 7292, 7324. Other notable, albeit weaker, emission lines include Mg I] lambda 4571, [Fe ii] lambda 7155, O I lambda 7774, Ca II triplet, and a broad, boxy feature at the location of H alpha. Unlike in other stripped-envelope SNe, the [O i] doublet is clearly resolved due to the presence of strong narrow components. The doublet shows an unprecedented emission line profile consisting of at least three components for each [O i]lambda 6300, 6364 line: a broad component (width similar to 2000 km s(-1)), and a pair of narrow blue and red components (width similar to 300 km s(-1)) mirrored against the rest velocity. The narrow component appears also in other lines, and is conspicuous in [O i]. This indicates the presence of multiple distinct kinematic components of material at low and high velocities. The low-velocity components are likely to be produced by a dense, slow-moving emitting region near the center, while the broad components are emitted over a larger volume. These observations suggest an asymmetric explosion, supporting the idea of two-component ejecta that influence the resulting late-time spectra and light curves. SN 2016gkg thus presents striking evidence for significant asymmetry in a standard-energy SN explosion. The presence of material at low velocity, which is not predicted in 1D simulations, emphasizes the importance of multidimensional explosion modeling of SNe

Ca2+ Cycling in Heart Cells from Ground Squirrels: Adaptive Strategies for Intracellular Ca2+ Homeostasis

Heart tissues from hibernating mammals, such as ground squirrels, are able to endure hypothermia, hypoxia and other extreme insulting factors that are fatal for human and nonhibernating mammals. This study was designed to understand adaptive mechanisms involved in intracellular Ca2+ homeostasis in cardiomyocytes from the mammalian hibernator, ground squirrel, compared to rat. Electrophysiological and confocal imaging experiments showed that the voltage-dependence of L-type Ca2+ current (ICa) was shifted to higher potentials in ventricular myocytes from ground squirrels vs. rats. The elevated threshold of ICa did not compromise the Ca2+-induced Ca2+ release, because a higher depolarization rate and a longer duration of action potential compensated the voltage shift of ICa. Both the caffeine-sensitive and caffeine-resistant components of cytosolic Ca2+ removal were more rapid in ground squirrels. Ca2+ sparks in ground squirrels exhibited larger amplitude/size and much lower frequency than in rats. Due to the high ICa threshold, low SR Ca2+ leak and rapid cytosolic Ca2+ clearance, heart cells from ground squirrels exhibited better capability in maintaining intracellular Ca2+ homeostasis than those from rats and other nonhibernating mammals. These findings not only reveal adaptive mechanisms of hibernation, but also provide novel strategies against Ca2+ overload-related heart diseases

Does chemotherapy-induced neutropaenia result in a postponement of adjuvant or neoadjuvant regimens in breast cancer patients? Results of a retrospective analysis

In 2005, 224 patients received adjuvant/neoadjuvant chemotherapy for breast cancer in a single institution according to daily practices. Regimens consisted of epirubicin-based chemotherapy (FEC100, four or six cycles), or three cycles of FEC100 followed by three cycles of docetaxel. An absolute blood count was carried out every 3 weeks, 1–3 days before planned chemotherapy cycle. Overall, 1238 cycles were delivered. An absolute neutrophil count (ANC) <1.5 × 109 l−1 before planned chemotherapy was found in 171 cycles. Of these, 130 cycles (76%) were delivered as planned regardless of whether ANC levels recovered, and 41 (24%) were delayed. None of these patients developed a febrile neutropaenia. Haematopoietic support (granulocyte colony-stimulating factor (G-CSF)) was required in 12 cycles. We found that the majority of patients with an ANC <1.5 × 109 l−1 before planned chemotherapy received planned doses, without complications and need for G-CSF

Cranial Pathologies in a Specimen of Pachycephalosaurus

. The specimen features two large oval depressions on the dorsal surface, accompanied by numerous circular pits on the margin and inner surface of the larger depressions.In order to identify the origin of these structures, computed tomography (CT) data and morphological characteristics of the specimen are analyzed and compared with similar osteological structures in fossil and extant archosaurs caused by taphonomic processes, non-pathologic bone resorption, and traumatic infection/inflammatory origins. The results of these analyses suggest that the structures are pathologic lesions likely resulting from a traumatic injury and followed by secondary infection at the site.The presence of lesions on a frontoparietal dome, and the exclusivity of their distribution along the dorsal dome surface, offers further insight into frontoparietal dome function and supports previously hypothesized agonistic behavior in pachycephalosaurids

A characterization of ASAS-SN core-collapse supernova environments with VLT+MUSE I. Sample selection, analysis of local environments, and correlations with light curve properties

The analysis of core-collapse supernova (CCSN) environments can provide important information on the life cycle of massive stars and constrain the progenitor properties of these powerful explosions. The MUSE instrument at the Very Large Telescope (VLT) enables detailed local environment constraints of the progenitors of large samples of CCSNe. Using a homogeneous SN sample from the All-Sky Automated Survey for Supernovae (ASAS-SN) survey, an untargeted and spectroscopically complete transient survey, has enabled us to perform a minimally biased statistical analysis of CCSN environments. Aims. We analyze 111 galaxies observed by MUSE that hosted 112 CCSNe-78 II, nine IIn, seven IIb, four Ic, seven Ib, three Ibn, two Ic-BL, one ambiguous Ibc, and one superluminous SN-detected or discovered by the ASAS-SN survey between 2014 and 2018. The majority of the galaxies were observed by the All-weather MUse Supernova Integral field Nearby Galaxies (AMUSING) survey. Here we analyze the immediate environment around the SN locations and compare the properties between the different CCSN types and their light curves. Methods. We used stellar population synthesis and spectral fitting techniques to derive physical parameters for all H ¯II regions detected within each galaxy, including the star formation rate (SFR), Hα equivalent width (EW), oxygen abundance, and extinction. Results. We found that stripped-envelope supernovae (SESNe) occur in environments with a higher median SFR, Hα EW, and oxygen abundances than SNe II and SNe IIn/Ibn. Most of the distributions have no statistically significant differences, except between oxygen abundance distributions of SESNe and SNe II, and between Hα EW distributions of SESNe and SNe II. The distributions of SNe II and IIn are very similar, indicating that these events explode in similar environments. For the SESNe, SNe Ic have higher median SFRs, Hα EWs, and oxygen abundances than SNe Ib. SNe IIb have environments with similar SFRs and Hα EWs to SNe Ib, and similar oxygen abundances to SNe Ic. We also show that the postmaximum decline rate, s, of SNe II correlates with the Hα EW, and that the luminosity and the Δ m15 parameter of SESNe correlate with the oxygen abundance, Hα EW, and SFR at their environments. This suggests a connection between the explosion mechanisms of these events to their environment properties

Regulator of G Protein Signaling 3 Modulates Wnt5b Calcium Dynamics and Somite Patterning

Vertebrate development requires communication among cells of the embryo in order to define the body axis, and the Wnt-signaling network plays a key role in axis formation as well as in a vast array of other cellular processes. One arm of the Wnt-signaling network, the non-canonical Wnt pathway, mediates intracellular calcium release via activation of heterotrimeric G proteins. Regulator of G protein Signaling (RGS) proteins can accelerate inactivation of G proteins by acting as G protein GTPase-activating proteins (GAPs), however, the possible role of RGS proteins in non-canonical Wnt signaling and development is not known. Here, we identify rgs3 as having an overlapping expression pattern with wnt5b in zebrafish and reveal that individual knockdown of either rgs3 or wnt5b gene function produces similar somite patterning defects. Additionally, we describe endogenous calcium release dynamics in developing zebrafish somites and determine that both rgs3 and wnt5b function are required for appropriate frequency and amplitude of calcium release activity. Using rescue of gene knockdown and in vivo calcium imaging assays, we demonstrate that the activity of Rgs3 requires its ability to interact with Gα subunits and function as a G protein GAP. Thus, Rgs3 function is necessary for appropriate frequency and amplitude of calcium release during somitogenesis and is downstream of Wnt5 activity. These results provide the first evidence for an essential developmental role of RGS proteins in modulating the duration of non-canonical Wnt signaling

Under the Skin of a Lion: Unique Evidence of Upper Paleolithic Exploitation and Use of Cave Lion (Panthera spelaea) from the Lower Gallery of La Garma (Spain)

ABSTRACT: Pleistocene skinning and exploitation of carnivore furs have been previously inferred from archaeological evidence. Nevertheless, the evidence of skinning and fur processing tends to be weak and the interpretations are not strongly sustained by the archaeological record. In the present paper, we analyze unique evidence of patterned anthropic modification and skeletal representation of fossil remains of cave lion (Panthera spelaea) from the Lower Gallery of La Garma (Cantabria, Spain). This site is one of the few that provides Pleistocene examples of lion exploitation by humans. Our archaeozoological study suggests that lion-specialized pelt exploitation and use might have been related to ritual activities during the Middle Magdalenian period (ca. 14800 cal BC). Moreover, the specimens also represent the southernmost European and the latest evidence of cave lion exploitation in Iberia. Therefore, the study seeks to provide alternative explanations for lion extinction in Eurasia and argues for a role of hunting as a factor to take into account

A kilonova as the electromagnetic counterpart to a gravitational-wave source

Gravitational waves were discovered with the detection of binary black-hole mergers1 and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova2,3,4,5. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate6. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst7,8. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of −1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90–140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process element

Contraindications of sentinel lymph node biopsy: Áre there any really?

BACKGROUND: One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient. METHODS: In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery. RESULTS: Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure. CONCLUSION: When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer