Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients

<br>Background:Prostate cancer cell growth is dependent upon androgen receptor (AR) activation, which is regulated by specific kinases. The aim of the current study is to establish if AR phosphorylation by Cdk1 or ERK1/2 is of prognostic significance.</br> <br>Methods: Scansite 2.0 was utilised to predict which AR sites are phosphorylated by Cdk1 and ERK1/2. Immunohistochemistry for these sites was then performed on 90 hormone-naive prostate cancer specimens. The interaction between Cdk1/ERK1/2 and AR phosphorylation was investigated in vitro using LNCaP cells.</br><br>Results:Phosphorylation of AR at serine 515 (pAR(S515)) and PSA at diagnosis were independently associated with decreased time to biochemical relapse. Cdk1 and pCdk1(161), but not ERK1/2, correlated with pAR(S515). High expression of pAR(S515) in patients with a PSA at diagnosis of ≤20 ng ml(-1) was associated with shorter time to biochemical relapse (P=0.019). This translated into a reduction in disease-specific survival (10-year survival, 38.1% vs 100%, P<0.001). In vitro studies demonstrated that treatment with Roscovitine (a Cdk inhibitor) caused a reduction in pCdk1(161) expression, pAR(S515)expression and cellular proliferation.</br> <br>Conclusion: In prostate cancer patients with PSA at diagnosis of ≤20 ng ml(-1), phosphorylation of AR at serine 515 by Cdk1 may be an independent prognostic marker.</br&gt

A Self-Reference False Memory Effect in the DRM Paradigm: Evidence from Eastern and Western Samples

It is well established that processing information in relation to oneself (i.e., selfreferencing) leads to better memory for that information than processing that same information in relation to others (i.e., other-referencing). However, it is unknown whether self-referencing also leads to more false memories than other-referencing. In the current two experiments with European and East Asian samples, we presented participants the Deese-Roediger/McDermott (DRM) lists together with their own name or other people’s name (i.e., “Trump” in Experiment 1 and “Li Ming” in Experiment 2). We found consistent results across the two experiments; that is, in the self-reference condition, participants had higher true and false memory rates compared to those in the other-reference condition. Moreover, we found that selfreferencing did not exhibit superior mnemonic advantage in terms of net accuracy compared to other-referencing and neutral conditions. These findings are discussed in terms of theoretical frameworks such as spreading activation theories and the fuzzytrace theory. We propose that our results reflect the adaptive nature of memory in the sense that cognitive processes that increase mnemonic efficiency may also increase susceptibility to associative false memories

Effect of varied shoot/root ratio on growth of maize (Zea mays) under nitrogen-limited conditions: growth experiment and model calculations

Young maize plants have been grown for two weeks on a perlite/sand mixture under controlled high light conditions at two suboptimal nitrogen levels. The relationships between [1] root dry weight (RDW) and dry weight of the total plants, [2] RDW and total root length (TRL), and [3] TRL and daily N-uptake during the two weeks were different for the two N-levels. In contrast, the relationships between [4] the N-concentrations in shoots (NCS) and in total plants, [5] shoot dry weight and leaf area, and [6] NCS and net assimilation rate (NAR) were similar at both N-levels. Mathematical descriptions of the six experimentally derived relationships were combined in a growth model. Varying relation [1] in the model allowed predictions about the effect of different shoot /root ratio (SRR) on growth. Both experimentally observed SRR-relations were nearly optimal for the respective N-levels. Therefore,the SRR established by the plants was close to the 'functional equilibrium' proposed for root and shoot growth

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

Brain computer tomography in critically ill patients -- a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients.</p> <p>Methods</p> <p>In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An “expected abnormality” was any finding that had been predicted by the physician requesting the brain CT. A brain CT was “diagnostically positive”, if the abnormality found was new or if an already known abnormality was increased. It was “diagnostically negative” if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as “treatment as planned”, “treatment changed, not as planned”, “treatment unchanged”.</p> <p>Results</p> <p>Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), <it>p</it> 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned.</p> <p>Conclusions</p> <p>The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.</p

From clump to disc scales in W3 IRS4 A case study of the IRAM NOEMA large programme CORE

Context. High-mass star formation typically takes place in a crowded environment, with a higher likelihood of young forming stars affecting and being affected by their surroundings and neighbours, as well as links between different physical scales affecting the outcome. However, observational studies are often focused on either clump or disc scales exclusively. Aims. We explore the physical and chemical links between clump and disc scales in the high-mass star formation region W3 IRS4, a region that contains a number of different evolutionary phases in the high-mass star formation process, as a case-study for what can be achieved as part of the IRAM NOrthern Extended Millimeter Array (NOEMA) large programme named CORE: “Fragmentation and disc formation in high-mass star formation”. Methods. We present 1.4 mm continuum and molecular line observations with the IRAM NOEMA interferometer and 30 m telescope, which together probe spatial scales from ~0.3−20′′ (600−40 000 AU or 0.003−0.2 pc at 2 kpc, the distance to W3). As part of our analysis, we used XCLASS to constrain the temperature, column density, velocity, and line-width of the molecular emission lines. Results. The W3 IRS4 region includes a cold filament and cold cores, a massive young stellar object (MYSO) embedded in a hot core, and a more evolved ultra-compact (UC)H II region, with some degree of interaction between all components of the region that affects their evolution. A large velocity gradient is seen in the filament, suggesting infall of material towards the hot core at a rate of 10−3−10−4 M⊙ yr−1, while the swept up gas ring in the photodissociation region around the UCH II region may be squeezing the hot core from the other side. There are no clear indications of a disc around the MYSO down to the resolution of the observations (600 AU). A total of 21 molecules are detected, with the abundances and abundance ratios indicating that many molecules were formed in the ice mantles of dust grains at cooler temperatures, below the freeze-out temperature of CO (≲35 K). This contrasts with the current bulk temperature of ~50 K, which was obtained from H2CO. Conclusions. CORE observations allow us to comprehensively link the different structures in the W3 IRS4 region for the first time. Our results argue that the dynamics and environment around the MYSO W3 IRS4 have a significant impact on its evolution. This context would be missing if only high resolution or continuum observations were available

Core fragmentation and Toomre stability analysis of W3(H2O): A case study of the IRAM NOEMA large program CORE

The fragmentation mode of high-mass molecular clumps and the properties of the central rotating structures surrounding the most luminous objects have yet to be comprehensively characterised. Using the IRAM NOrthern Extended Millimeter Array (NOEMA) and the IRAM 30-m telescope, the CORE survey has obtained high-resolution observations of 20 well-known highly luminous star-forming regions in the 1.37 mm wavelength regime in both line and dust continuum emission. We present the spectral line setup of the CORE survey and a case study for W3(H2O). At ~0.35" (700 AU at 2 kpc) resolution, the W3(H2O) clump fragments into two cores (West and East), separated by ~2300 AU. Velocity shifts of a few km/s are observed in the dense-gas tracer, CH3CN, across both cores, consistent with rotation and perpendicular to the directions of two bipolar outflows, one emanating from each core. The kinematics of the rotating structure about W3(H2O) W shows signs of differential rotation of material, possibly in a disk-like object. The observed rotational signature around W3(H2O) E may be due to a disk-like object, an unresolved binary (or multiple) system, or a combination of both. We fit the emission of CH3CN (12-11) K = 4-6 and derive a gas temperature map with a median temperature of ~165 K across W3(H2O). We create a Toomre Q map to study the stability of the rotating structures against gravitational instability. The rotating structures appear to be Toomre unstable close to their outer boundaries, with a possibility of further fragmentation in the differentially-rotating core W3(H2O) W. Rapid cooling in the Toomre-unstable regions supports the fragmentation scenario. Combining millimeter dust continuum and spectral line data toward the famous high-mass star-forming region W3(H2O), we identify core fragmentation on large scales, and indications for possible disk fragmentation on smaller spatial scales

Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

<p>Abstract</p> <p>Background</p> <p>The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality.</p> <p>Methods/Design</p> <p>We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥10⁵ colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥10⁵ CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs.</p> <p>Discussion</p> <p>This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment.</p> <p>Trial registration</p> <p>Dutch trial registry: NTR-3068</p