Search

This systematic review aims to identify the demographic, clinical and psychological factors associated with post-traumatic growth (PTG) in parents following their child's admission to the intensive care unit (ICU). Papers published up to September 2021 were identified following a search of electronic databases (PubMed, Medline, Web of Science, PsycINFO, CINAHL, PTSDpubs and EMBASE). Studies were included if they involved a sample of parents whose children were previously admitted to ICU and reported correlational data. 1777 papers were reviewed. Fourteen studies were eligible for inclusion; four were deemed to be of good methodological quality, two were poor, and the remaining eight studies were fair. Factors associated with PTG were identified. Mothers, and parents of older children, experienced greater PTG. Parents who perceived their child's illness as more severe had greater PTG. Strong associations were uncovered between PTG and post-traumatic stress, psychological well-being and coping. PTG is commonly experienced by this population. Psychological factors are more commonly associated with PTG in comparison with demographic and clinical factors, suggesting that parents' subjective ICU experience may be greater associated with PTG than the objective reality. [ABSTRACT FROM AUTHOR]

Disclosing an epilepsy diagnosis to others is complex due to the condition's largely invisible nature and associated stigma. Despite this, little has been documented in terms of what this process involves for children living with epilepsy (CWE) and their parents. A systematic review was conducted to examine and synthesize evidence pertaining to: (i) the disclosure practices of CWE and their parents, (ii) enablers and barriers for disclosure, (iii) the impact of disclosure practices, and (iv) the relationship between disclosure management and other variables. The electronic databases PsycINFO, PubMed, MEDLINE, CINAHL, Scopus, and Web of Science were searched systematically. Any empirical, peer-reviewed journal articles with findings reported regarding the self- or proxy-reported disclosure practices of children aged 0–18 years with any type of epilepsy and/or their parents were deemed eligible for inclusion. Two review authors completed all stages of screening, data extraction, and quality assessment independently with two additional review authors resolving any discrepancies. A total of 32 articles were included in the review. Only one dated study examined disclosure as a primary focus; in the remaining studies, disclosure was a subfocus of larger studies or pertinent qualitative themes/subthemes incidentally emerged. The limited evidence suggests that: 1) CWE and parents adopt varying disclosure management strategies — from concealment to voluntary disclosure; 2) disclosure decisions are challenging for CWE and parents; 3) many barriers to disclosure exist (e.g., fear of stigmatization and rejection); 4) only a limited number of factors that enable disclosure are known (e.g., openness by others to engage with and learn about epilepsy); 5) disclosure management is significantly related to a number of variables (e.g., child/maternal perceived stigma and seizure control); and 6) there are varying outcomes for CWE and/or their parents in accordance with the adoption of specific disclosure management strategies (e.g., disclosure resulting in greater acceptance and the receipt of support or evoking anxiety/fear in others; and concealment resulting in misunderstandings, embarrassment, and stigma-coaching), but the evidence remains inconclusive in terms of which disclosure management strategy is optimal. While some preliminary work has been conducted, disclosure of epilepsy is a topic that has been largely neglected to date. This is despite the fact that disclosure is a significant source of concern for CWE and parent populations. Future studies should focus on elucidating the unique contextual factors that inform disclosure decisions in order to develop a theoretical framework that can explain the epilepsy disclosure decision-making process. [ABSTRACT FROM AUTHOR]

In childhood chronic illness, family communication can impact the child's and parents' psychosocial well-being. However, little is known about family communication in the context of epilepsy in childhood. The aim of this systematic review was to identify the existing evidence available on communication strategies adopted by families living with childhood epilepsy, including; the facilitators, barriers and challenges experienced by families when choosing to communicate, or not, about epilepsy; and the consequences of this communication. Papers published in the English language prior to March 2015 were identified following a search of six electronic databases: PubMed, MEDLINE, Web of Science, PsycINFO, CINAHL, and Scopus. Studies were included if they involved a sample of parents of children with epilepsy or children/young people with epilepsy (0–18 years of age) and used qualitative, quantitative, or mixed methods. Following a comprehensive search and screening process, 26 studies were identified as eligible for inclusion in the review. No studies identified specific communication strategies adopted by families living with childhood epilepsy. Some studies found that talking about epilepsy with family members had positive consequences (e.g., communication as an effective coping strategy), with no negative consequences reported in any of the studies. The main barrier to communication for parents was an unwillingness to use the word “epilepsy” because of the perceived negative social connotations associated with the health condition. For children with epilepsy, barriers were as follows: parental desire to keep epilepsy a secret, parents' tendency to deny that the child had epilepsy, parental overprotection, and parents' tendency to impose greater restrictions on the child with epilepsy than on siblings without epilepsy. Future research investigating the communication strategies of families living with epilepsy is needed in order to create effective communication-based interventions for discussing epilepsy within the home. [ABSTRACT FROM AUTHOR]

Purpose: The diagnosis of children with disorders of sex development (DSD) requires a karyotype, different biochemical and radiological investigations in the context of a multidisciplinary team. The aim of this study was to compare the diagnostic accuracy of laparoscopy (L) versus ultrasonography (US) in the assessment of children with complex DSD. Methods: We retrospectively examined the theatre database searching for children with DSD who underwent laparoscopic surgery from 1999 to 2011. The medical and radiological records were reviewed. Results: Eighteen patients were identified. Age at diagnosis ranged from birth to 14 years (mean 2.5 years). There were seven patients with 46XY dysgenetic testicular DSD (4 mosaic Turner, 3 mixed gonadal dysgenesis), seven patients with 46XY non-dysgenetic testicular DSD (4 persistent Mullerian duct syndrome, 2 complete androgen insensitivity syndrome, one unknown), two patients with ovotesticular DSD, one patient with 46XX DSD (congenital adrenal hyperplasia) and one patient with 46XY DSD complete sex reversal. Fifteen underwent ultrasonography prior to laparoscopy. Both modalities identified Mullerian structures in seven (47 %) patients, in one (7 %) patient US and L confirmed the absence of Mullerian structures, while in six (40 %) patients there was discordance, with US failing to visualize pelvic Mullerian structures. In the last patient with 46XY non-dysgenetic testicular DSD, the rectum was thought to be a dilated uterus on ultrasonography. Conclusions: Pelvic ultrasonography failed to identify Mullerian structures in 40 % of patients with complex DSD. On the contrary, laparoscopy allowed excellent visualization of pelvic structures and gonads in children with complex DSD. [ABSTRACT FROM AUTHOR]

We present a preliminary analysis of the sensitivity of Anglo-Australian Planet Search data to the orbital parameters of extrasolar planets. To do so, we have developed new tools for the automatic analysis of large-scale simulations of Doppler velocity planet search data. One of these tools is the two-dimensional Keplerian Lomb–Scargle (LS) periodogram that enables the straightforward detection of exoplanets with high eccentricities (something the standard LS periodogram routinely fails to do). We used this technique to redetermine the orbital parameters of HD 20782b, with one of the highest known exoplanet eccentricities . We also derive a set of detection criteria that do not depend on the distribution functions of fitted Keplerian orbital parameters (which we show are non-Gaussian with pronounced, extended wings). Using these tools, we examine the selection functions in orbital period, eccentricity and planet mass of Anglo-Australian Planet Search data for three planets with large-scale Monte Carlo like simulations. We find that the detectability of exoplanets declines at high eccentricities. However, we also find that exoplanet detectability is a strong function of epoch-to-epoch data quality, number of observations and period sampling. This strongly suggests that simple parametrizations of the detectability of exoplanets based on ‘whole-of-survey’ metrics may not be accurate. We have derived empirical relationships between the uncertainty estimates for orbital parameters that are derived from least-squares Keplerian fits to our simulations and the true 99 per cent limits for the errors in those parameters, which are larger than equivalent Gaussian limits by the factors of 5–10. We quantify the rate at which false positives are made by our detection criteria, and find that they do not significantly affect our final conclusions. And finally, we find that there is a bias against measuring near-zero eccentricities, which becomes more significant in small, or low signal-to-noise ratio, data sets. [ABSTRACT FROM AUTHOR]

We present a quantitative investigation of the effect of stellar oscillations on Doppler velocity planet searches. Using data from four asteroseismological observation campaigns, we find a power-law relationship between the noise impact of these oscillations on Doppler velocities and both the luminosity-to-mass of the target stars, and observed integration times. Including the impact of oscillation, jitter should improve the quality of Keplerian fits to Doppler velocity data. The scale of the effect these oscillations have on Doppler velocity measurements is smaller than that produced by stellar activity, but is most significant for giant and subgiant stars, and at short integration times (i.e. less than a few minutes). Such short observation times tend to be used only for very bright stars. However, since it is these very same stars that tend to be targeted for the highest precision observations, as planet searches probe to lower and lower planet masses, oscillation noise for these stars can be significant and needs to be accounted for in observing strategies. [ABSTRACT FROM AUTHOR]

We present the initial results of an abundance analysis of echelle UV spectra of five hot subdwarf B (sdB) stars. These stars have been identified as core helium burning objects on the extreme Horizontal Branch. Around 5% of sdBs show short-period acoustic-mode oscillations. Models predict that these oscillations are due to an opacity bump caused by the ionisation of iron group elements. The necessary metal abundance has to be maintained by diffusive equilibrium between gravitational settling and radiative levitation. However, analyses of high-resolution optical spectra has revealed that we cannot discriminate between pulsating and non-pulsating sdBs on the basis of the surface iron abundance. We have therefore obtained HST/STIS observations of three pulsators and two non-pulsators in the near- and far-UV to measure the surface abundance of elements that are unobservable from the ground. The overall aim of our study is to test diffusion and pulsation calculations by searching for significant differences between these surface abundances. [ABSTRACT FROM AUTHOR]

ABSTRACT We present the detection and analysis of line index variations in the pulsating sdB star PG 1605+072. We have found a strong dependence of line index amplitude on Balmer line order, with high-order Balmer line amplitudes up to 10 times larger than Hβ. Using a simple model, we have found that the line index may not only be dependent on temperature, as is usually assumed for oscillating stars, but also on surface gravity. This information will provide another set of observables that can be used for mode identification of sdBs. [ABSTRACT FROM AUTHOR]

Giant planets on long-period orbits around the nearest stars are among the easiest to directly image. Unfortunately these planets are difficult to fully constrain by indirect methods, e.g. transit and radial velocity (RV). In this study, we present the discovery of a super-Jupiter, HD 222237 b, orbiting a star located |$11.445\pm 0.002$|  pc away. By combining RV data, Hipparcos , and multi-epoch Gaia astrometry, we estimate the planetary mass to be |${5.19}_{-0.58}^{+0.58}\, M_{\rm Jup}$|⁠ , with an eccentricity of |${0.56}_{-0.03}^{+0.03}$| and a period of |${40.8}_{-4.5}^{+5.8}$|  yr, making HD 222237 b a promising target for imaging using the Mid-Infrared Instrument (MIRI) of JWST. A comparative analysis suggests that our method can break the inclination degeneracy and thus differentiate between prograde and retrograde orbits of a companion. We further find that the inferred contrast ratio between the planet and the host star in the F 1550 C filter (⁠|$15.50\, \mu \rm m$|⁠) is approximately |$1.9\times 10^{-4}$|⁠ , which is comparable with the measured limit of the MIRI coronagraphs. The relatively low metallicity of the host star (⁠|$\rm -0.32\, dex$|⁠) combined with the unique orbital architecture of this system presents an excellent opportunity to probe the planet–metallicity correlation and the formation scenarios of giant planets. [ABSTRACT FROM AUTHOR]

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. [ABSTRACT FROM AUTHOR]

We have measured the orbital parameters of seven close binaries, including six new objects, in a radial velocity survey of 38 objects comprising a hot subdwarf star with orbital periods ranging from ~0.17 to 3 d. One new system, GALEX J2205-3141, shows reflection on an M dwarf companion. Three other objects show significant short-period variations, but their orbital parameters could not be constrained. Two systems comprising a hot subdwarf paired with a bright main-sequence/giant companion display short-period photometric variations possibly due to irradiation or stellar activity and are also short-period candidates. All except two candidates were drawn from a selection of subluminous stars in the Galaxy Evolution Explorer ultraviolet sky survey. Our new identifications also include a low-mass subdwarf B star and likely progenitor of a low-mass white dwarf (GALEX J0805-1058) paired with an unseen, possibly substellar, companion. The mass functions of the newly identified binaries imply minimum secondary masses ranging from 0.03 to 0.39M. Photometric time series suggest that, apart from GALEX J0805-1058 and J2205-3141, the companions are most likely white dwarfs. We update the binary population statistics: close to 40 per cent of hot subdwarfs have a companion. Also, we found that the secondary mass distribution shows a low-mass peak attributed to late-type dwarfs, and a higher mass peak and tail distribution attributed to white dwarfs and a few spectroscopic composites. Also, we found that the population kinematics imply an old age and include a few likely halo population members. [ABSTRACT FROM AUTHOR]

ABSTRACT We present follow-up observations of the pulsating subdwarf B (sdB) star EC 01541-1409 as part of our efforts to resolve pulsation spectra for use in asteroseismological analyses. This paper reports on data obtained from a single-site campaign, during 2008, and a multisite campaign, during 2009. From limited 2008 data, we were able to clearly resolve and pre-whiten 24 periods. A subsequent multisite campaign spanning nearly 2 months found over 30 individual periodicities most of which were unstable in amplitude and/or phase. Pulsation amplitudes were found to the detection limit, meaning that further observations would likely reveal more periodicities. EC 01541-1409 reveals itself to be one of two sdB pulsators with many pulsation frequencies covering a large frequency range. Unlike the other star of this type (PG 0048+091), it has one high-amplitude periodicity which appears phase stable, making EC 01541-1409 an excellent candidate for exoplanet studies via pulsation phases. No multiplets were detected leaving EC 01541-1409 as yet another rich p-mode sdB pulsator without these features, limiting observational constraints on pulsation modes. [ABSTRACT FROM AUTHOR]

Recognition of the pivotal role of estrogen in the aetiology of breast cancer has led to the development of antiestrogens (AE), such as tamoxifen (TAM) as effective therapies for the treatment and prevention of this disease. However, despite their widespread clinical efficacy, response to AEs is often short-lived, and acquired or innate therapeutic resistance remains a major obstacle in the successful treatment of breast cancer. Thus, delineating the intracellular pathways that mediate the cellular response to estrogen could potentially lead to new, more effective approaches to the treatment of breast cancer, particularly endocrine-resistant disease. Here, we have identified the BCL-2 homology 3 (BH3)-only, pro-apoptotic regulator, PUMA (p53 upregulated modulator of apoptosis) as an estrogen target gene that is acutely downregulated in response to estrogen in breast cancer cell lines, independently of their p53 status. PUMA is transcriptionally upregulated following treatment with TAM, and knock down of PUMA expression in these cells attenuates the apoptotic response to TAM. Furthermore, low PUMA expression in breast carcinomas is significantly associated with breast cancer-specific death (P=0.0014 and P=0.0115, for mRNA and protein, respectively), and worse outcome in TAM-treated patients (mRNA, P=1.49e-05). These findings suggest that the dysregulation of apoptotic signaling pathways such as those executed through PUMA, can significantly impact on both the progression and therapeutic responsiveness of breast cancer. Moreover, they provide a convincing rationale for exploring new therapeutic approaches involving endocrine and non-endocrine therapies that target apoptotic pathways as an effective strategy for tackling endocrine refractory disease. [ABSTRACT FROM AUTHOR]

In this paper, we show that method of mode identification using combined multicolour photometry and spectroscopy can be successfully applied to the pulsating subdwarf B star Balloon 090100001. The method constrains the spherical degree, ℓ. We confirm that the dominant mode is radial and we show that for some other modes the method provides values of ℓ consistent with the observed rotationally split triplet. Moreover, we derive a radius variation of 1.7 per cent for the dominant mode. The identification opens the possibility for constraining the internal structure of the star by means of seismic methods. [ABSTRACT FROM AUTHOR]

Objective To observe the outcome in a group of children with undescended testes (UDT) given prolonged human chorionic gonadotrophin (hCG) stimulation as part of their management. Study design Retrospective review of 16 prepubertal boys given intramuscular hCG, 1500 U, on Days 1, 2 and 3 and then twice a week for 2 weeks with assessment of serum testosterone (T), SHBG, dihydrotestosterone (DHT) and androstenedione (A) on Days 1, 4 and 22. Results In seven boys (44%), peak rise in T was by Day 4; in 5 boys (31%), the rise was by Day 22 and in the remainder, serum T stayed low. The median Day1 testosterone : androstenedione (T : A) ratio rose from 0·4 (range 0·2–1·5) to 1·7 (range 0·2–5·3) at Day 4 ( P < 0·05) with no further rise by Day 22. The median dihydrotestosterone : testosterone ratio (DHT : T) at Day 1 and Day 4 remained unchanged. SHBG levels were more likely to be lower at Day 22 than at Day 4. The mean testosterone : SHBG (T : SHBG) ratio as a marker of androgen sensitivity was 0·2 (1SD 0·1). Bilateral testicular descent deemed immediate surgery unnecessary in 3 out of 15 (20%) boys where outcome data were available. Conclusion Whilst a 3-day hCG stimulation regimen may exclude 17β-hydroxysteroid dehydrogenase-3 and 5α-reductase deficiencies, some boys with cryptorchidism may require more prolonged stimulation to assess androgen production and sensitivity. The possibility that this regimen leads to a reduced need for orchidopexy requires further exploration. [ABSTRACT FROM AUTHOR]

An important characteristic of silicon-based particle detectors, such as those used for the forthcoming ATLAS ITk upgrade for the HL-LHC, is the leakage current. This characteristic is evaluated in the quality control stage of the new ITk strip sensors by performing an IV measurement, where the sensors are biased up to − 700 V , typically showing low and stable leakage current. However, some sensors can exhibit a sudden leakage current increase during the IV measurement, so-called early breakdown, making the sensor unusable. The analysis of these early breakdown conditions typically consists of visual inspection of the sensors using a microscope, as often this is caused by physical damage, such as a deep scratch, chipping on the edges of the sensor, or other damage. However, the association of the observed damage with the early breakdown is not definitive. Rather, this is an association by correlation, due to the limits of verification by observation with standard equipment. A hot spot imaging setup has proven to be a valuable diagnostic tool to identify and understand these early breakdown conditions and elaborate on former understandings of these emissions. The regions responsible for the breakdown can be properly located by imaging the near infra-red light emissions produced by them in breakdown conditions. These regions of interest can also be imaged at magnification to evaluate the more precise structure of the breakdown to better understand the damage. The regions discovered, which have improved our understanding of breakdown damage and its symptoms, include scratches, chipping, static charge buildup and fabrication defects in the ATLAS18 strip sensors and test structures. [ABSTRACT FROM AUTHOR]

In this study, we identify 11 Kepler systems (KIC 5255552, 5653126, 5731312, 7670617, 7821010, 8023317, 10268809, 10296163, 11519226, 11558882, and 12356914) with a flip-flop effect in the eclipse timing variations O − C diagrams of the systems, report on what these systems have in common and whether these systems are dynamically stable. These systems have previously reported high eccentric binary stars with highly eccentric third bodies/outer companions. We find that all of the additional bodies in the system are dynamically stable for the configurations previously reported and are therefore likely to exist as described. We also provide additional evidence of KIC 5255552 being a quadruple star system composed of an eclipsing binary pair and non-eclipsing binary pair with the possibility of a fifth body in the system. With the advent of the NASA's Transiting Exoplanet Survey Satellite (TESS) exoplanet survey, its precision photometric monitoring offers an opportunity to help confirm more local eclipsing binary star companions, including planets. [ABSTRACT FROM AUTHOR]

Our understanding of planetary systems different to our own has grown dramatically in the past 30 yr. However, our efforts to ascertain the degree to which the Solar system is abnormal or unique have been hindered by the observational biases inherent to the methods that have yielded the greatest exoplanet hauls. On the basis of such surveys, one might consider our planetary system highly unusual – but the reality is that we are only now beginning to uncover the true picture. In this work, we use the full 18-yr archive of data from the Anglo-Australian Planet Search to examine the abundance of 'cool Jupiters' – analogues to the Solar system's giant planets, Jupiter and Saturn. We find that such planets are intrinsically far more common through the cosmos than their siblings, the hot Jupiters. We find that the occurrence rate of such 'cool Jupiters' is |$6.73^{+2.09}_{-1.13}$|  per cent, almost an order of magnitude higher than the occurrence of hot Jupiters (at |$0.84^{+0.70}_{-0.20}$|  per cent). We also find that the occurrence rate of giant planets is essentially constant beyond orbital distances of ∼1 au. Our results reinforce the importance of legacy radial velocity surveys for the understanding of the Solar system's place in the cosmos. [ABSTRACT FROM AUTHOR]

In this paper, we report the evidence for a planetary mass body orbiting the close binary star KIC 5095269. This detection arose from a search for eclipse timing variations amongst the more than 2000 eclipsing binaries observed by Kepler. Light curve and periodic eclipse time variations have been analysed using SYSTEMIC and a custom BINARY ECLIPSE TIMINGS code based on the TRANSIT ANALYSIS PACKAGE which indicates a 7.70 ± 0.08MJup object orbiting every 237.7 ± 0.1 d around a 1.2M⊙ primary and a 0.51M⊙ secondary in an 18.6 d orbit. A dynamical integration over 107 yr suggests a stable orbital configuration. Radial velocity observations are recommended to confirm the properties of the binary star components and the planetary mass of the companion. [ABSTRACT FROM AUTHOR]

We report the detection of sixteen binary systems from the Anglo-Australian Planet Search. Solutions to the radial velocity data indicate that the stars have companions orbiting with a wide range of masses, eccentricities and periods. Three of the systems potentially contain brown-dwarf companions while another two have eccentricities that place them in the extreme upper tail of the eccentricity distribution for binaries with periods less than 1000 d. For periods up to 12 years, the distribution of our stellar companion masses is fairly flat, mirroring that seen in other radial velocity surveys, and contrasts sharply with the current distribution of candidate planetary masses, which rises strongly below 10 MJ. When looking at a larger sample of binaries that have FGK star primaries as a function of the primary star metallicity, we find that the distribution maintains a binary fraction of ~43 ± 4 per cent between -1.0 and +0.6 dex in metallicity. This is in stark contrast to the giant exoplanet distribution. This result is in good agreement with binary formation models that invoke fragmentation of a collapsing giant molecular cloud, suggesting that this is the dominant formation mechanism for close binaries and not fragmentation of the primary star's remnant protoplanetary disc. [ABSTRACT FROM AUTHOR]

The project Massive Unseen Companions to Hot Faint Underluminous Stars from SDSS (MUCHFUSS) aims to find sdBs with compact companions such as massive white dwarfs, neutron stars, or black holes. Here we provide classifications, atmospheric parameters, and a complete radial velocity (RV) catalogue containing 1914 single measurements for a sample of 177 hot subluminous stars discovered based on SDSS DR7; 110 stars show significant RV variability, while 67 qualify as candidates. We constrain the fraction of close massive compact companions of hydrogen-rich hot subdwarfs in our sample to be smaller than ~1.3%, which is already close to the theoretical predictions. However, the sample might still contain such binaries with longer periods exceeding ~8 d. We detect a mismatch between the ΔRVmax-distribution of the sdB and the more evolved sdOB and sdO stars, which challenges our understanding of their evolutionary connection. Furthermore, irregular RV variations of unknown origin with amplitudes of up to ~180 km s-1 on timescales of years, days, and even hours have been detected in some He-sdO stars. They might be connected to irregular photometric variations in some cases. [ABSTRACT FROM AUTHOR]

Aims Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations in IGF1R copy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases. Methods IGF1R gene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, including EGFR and KRAS mutational status and patient survival. Results IGF1R gene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibited IGF1R gene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation between IGF1R gene copy number and protein expression (r=0.2, p<0.05). Alterations of IGF1R gene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). High IGF1R gene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade, EGFR or KRAS mutational status or overall survival. Conclusions High IGF1R gene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant. [ABSTRACT FROM AUTHOR]

Background:The prognostic significance of BRAF and NRAS mutations in metastatic melanoma patients remains uncertain, with several studies reporting conflicting results, often biased by the inclusion of patients treated with BRAF and MEK (MAPK) inhibitors. We therefore interrogated a historical cohort of patients free of the confounding influence of MAPK inhibitor therapy.Methods:Patients with available archival tissue first diagnosed with metastatic melanoma between 2002 and 2006 were analysed. Mutational analysis was performed using the OncoCarta Panel. Patient characteristics, treatment outcome and survival were correlated with BRAF/NRAS mutation status.Results:In 193 patients, 92 (48%) melanomas were BRAF-mutant, 39 (20%) were NRAS-mutant and 62 (32%) were wild-type for BRAF/NRAS mutations (wt). There was no difference in response to chemotherapy based on mutation status (35-37%). The distant disease-free interval (DDFI) was significantly shorter in patients with wt melanoma (27.9 months vs 35.1 for BRAF and 49.1 for NRAS) although this was not significant in multivariate analysis. Survival from stage IV melanoma diagnosis was not significantly different based on mutation status. The DDFI was significantly shorter in patients with BRAFV600K/R versus BRAFV600E melanoma in univariate and multivariate analyses.Conclusions:BRAF and NRAS mutation status does not influence survival in metastatic melanoma. [ABSTRACT FROM AUTHOR]

Vemurafenib is a tyrosine kinase inhibitor of BRAF that prolongs survival in patients with BRAF V600-mutant metastatic melanoma. Secondary cutaneous malignancies are a well-documented toxicity of vemurafenib, thought to be mediated by enhanced ERK signalling in BRAF wild-type, RAS-mutant cells. Vemurafenib could also promote growth of non-cutaneous secondary malignancies by a similar mechanism. We present a case of an individual who received vemurafenib for metastatic melanoma and experienced rapid growth of a pre-existing KRAS -mutant pancreatic adenocarcinoma. [ABSTRACT FROM AUTHOR]

We present six years of new radial velocity data from the Anglo-Australian and Magellan Telescopes on the HD 73526 2:1 resonant planetary system. We investigate both Keplerian and dynamical (interacting) fits to these data, yielding four possible configurations for the system. The new data now show that both resonance angles are librating, with amplitudes of 40° and 60°, respectively. We then perform long-term dynamical stability tests to differentiate these solutions, which only differ significantly in the masses of the planets. We show that while there is no clearly preferred system inclination, the dynamical fit with i = 90° provides the best combination of goodness-of-fit and long-term dynamical stability. [ABSTRACT FROM AUTHOR]

Aim We assessed the diagnostic accuracy of epidermal growth factor receptor (EGFR) mutant-specific antibodies for detecting two common activating EGFR mutations. Methods Immunohistochemical expression of mutation-specific antibodies against EGFR exon 19 deletion E746-A750 ((c.2235_2249del15 or c.2236_2250del15, p. Glu746_Ala750del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg) were assessed in a cohort of 204 resected early stage node negative lung adenocarcinomas, and protein expression was compared with DNA analysis results from mass spectrometry analysis. Results Of seven cases with L858R point mutation, six were positive by immunohistochemistry (IHC). There were three false positive cases using L858R IHC (sensitivity 85.7%, specificity 98.5%, positive predictive value 66.7%, negative predictive value 99.5%). All seven E746-A750 exon 19 deletions identified by mutation analysis were positive by IHC. Four additional cases were positive for exon 19 IHC but negative by mutation analysis. The sensitivity of exon 19 IHC for E746-A750 was 100%, specificity 98.0%, positive predictive value 63.6% and negative predictive value 100%. Conclusions Mutant-specific EGFR IHC has good specificity and sensitivity for identifying targeted activating EGFR mutations. Although inferior to molecular genetic analysis of the EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations. The antibodies are likely to be of clinical value in cases where limited tumour material is available, or in situations where molecular genetic analysis is not readily available [ABSTRACT FROM AUTHOR]

Hot subdwarf B stars (sdBs) are evolved core helium-burning stars with very thin hydrogen envelopes. To form an sdB, the progenitor has to lose almost all of its hydrogen envelope right at the tip of the red giant branch. In close binary systems, mass transfer to the companion provides the extraordinary mass loss required for their formation. However, apparently single sdBs exist as well, and their formation has been unclear for decades. The merger of helium white dwarfs leading to an ignition of core helium-burning or the merger of a helium core and a low-mass star during the common envelope phase have been proposed. Here we report the discovery of SB290 as the first apparently single, fast-rotating sdB star located on the extreme horizontal branch, indicating that those stars may form from mergers. [ABSTRACT FROM AUTHOR]

Context. The abilities of radial velocity exoplanet surveys to detect the lowest-mass extra-solar planets are currently limited by a combination of instrument precision, lack of data, and "jitter". Jitter is a general term for any unknown features in the noise, and reflects a lack of detailed knowledge of stellar physics (asteroseismology, starspots, magnetic cycles, granulation, and other stellar surface phenomena), as well as the possible underestimation of instrument noise. Aims. We study an extensive set of radial velocities for the star HD 10700 (т Ceti) to determine the properties of the jitter arising from stellar surface inhomogeneities, activity, and telescope-instrument systems, and perform a comprehensive search for planetary signals in the radial velocities. Methods. We performed Bayesian comparisons of statistical models describing the radial velocity data to quantify the number of significant signals and the magnitude and properties of the excess noise in the data. We reached our goal by adding artificial signals to the "flat" radial velocity data of HD 10700 and by seeing which one of our statistical noise models receives the greatest posterior probabilities while still being able to extract the artificial signals correctly from the data. We utilised various noise components to assess properties of the noise in the data and analyse the HARPS, AAPS, and HIRES data for HD 10700 to quantify these properties and search for previously unknown low-amplitude Keplerian signals. Results. According to our analyses, moving average components with an exponential decay with a timescale from a few hours to few days, and Gaussian white noise explains the jitter the best for all three data sets. Fitting the corresponding noise parameters results in significant improvements of the statistical models and enables the detection of very weak signals with amplitudes below 1 ms-1 level in our numerical experiments. We detect significant periodicities that have no activity-induced counterparts in the combined radial velocities. Three of these signals can be seen in the HARPS data alone, and a further two can be inferred by utilising the AAPS and Keck data. These periodicities could be interpreted as corresponding to planets on dynamically stable close-circular orbits with periods of 13.9, 35.4, 94, 168, and 640 days and minimum masses of 2.0, 3.1, 3.6, 4.3, and 6.6 M⊕, respectively. [ABSTRACT FROM AUTHOR]

ABSTRACT We report the discovery of two new pulsating subdwarf B (sdB) stars in the open cluster NGC 6791 using data from the Kepler spacecraft. Three sdB stars were observed for one month in short-cadence (1 min) mode and three months in long-cadence (30 min) mode during Quarter 11 (fall 2011). The stars have Kepler Input Catalogue numbers of 2437937, 2569576 and 2569583 with previous designations of B5, B3 and B6, respectively. Another sdB star exists in the cluster and it is also known to be a pulsator. We also obtained Nordic Optical Telescope spectra to update effective temperatures, surface gravities and helium abundances and compare the spectroscopic properties of all four stars on a uniform model grid. We detect four periodicities between 0.9 and 2.4 h in B3 above a detection limit of 0.53 parts per thousand (ppt) and nine periodicities between 1.1 and 2.2 h in B5 above a detection limit of 0.37 ppt. No pulsations were detected in B6 to the detection threshold of 0.29 ppt. The long-cadence data were less useful as few observations are obtained per pulsation period, yet they do indicate that the pulsations are variable from month to month. The spacings between the pulsation periods are similar to other g-mode pulsating sdB stars observed by Kepler, indicating that the periodicities can be associated witquals; 1 modes. A fit to the periods give spacings of 234.6 ± 0.6 and 242.6 ± 1.5 s for B3 and B5, respectively. [ABSTRACT FROM AUTHOR]

ABSTRACT We present our analyses of 15 months of Kepler data on KIC 10139564. We detected 57 periodicities with a variety of properties not previously observed all together in one pulsating subdwarf B (sdB) star. Ten of the periodicities were found in the low-frequency region, and we associate them with nonradial g modes. The other periodicities were found in the high-frequency region, which are likely p modes. We discovered that most of the periodicities are components of multiplets with a common spacing. Assuming that multiplets are caused by rotation, we derive a rotation period of 25.6 ± 1.8 d. The multiplets also allow us to identify the pulsations to an unprecedented extent for this class of pulsator. We also detect l ≥ 2 multiplets, which are sensitive to the pulsation inclination and can constrain limb darkening via geometric cancellation factors. While most periodicities are stable, we detected several regions that show complex patterns. Detailed analyses showed that these regions are complicated by several factors. Two are combination frequencies that originate in the super-Nyquist region and were found to be reflected below the Nyquist frequency. The Fourier peaks are clear in the super-Nyquist region, but the orbital motion of Kepler smears the Nyquist frequency in the barycentric reference frame and this effect is passed on to the sub-Nyquist reflections. Others are likely multiplets but unstable in amplitudes and/or frequencies. The density of periodicities also makes KIC 10139564 challenging to explain using published models. This menagerie of properties should provide tight constraints on structural models, making this sdB star the most promising for applying asteroseismology. To support our photometric analysis, we have obtained spectroscopic radial-velocity measurements of KIC 10139564 using low-resolution spectra in the Balmer-line region. We did not find any radial-velocity variation. We used our high signal-to-noise average spectrum to improve the atmospheric parameters of the sdB star, deriving Teff = 31 859 K and log g = 5.673 dex. [ABSTRACT FROM AUTHOR]

ABSTRACT We have used 605 days of photometric data from the Kepler spacecraft to study KIC 6614501, a close binary system with an orbital period of 0.157 497 47(25) days (3.779 939 h), that consists of a low-mass subdwarf B (sdB) star and a white dwarf (WD). As seen in many other similar systems, the gravitational field of the WD produces an ellipsoidal deformation of the sdB which appears in the light curve as a modulation at two times the orbital frequency. The ellipsoidal deformation of the sdB implies that the system has a maximum inclination of ∼40°, with i ≈ 20° being the most likely. The orbital radial velocity (RV) of the sdB star is high enough to produce a Doppler beaming effect with an amplitude of 432 ± 5 ppm, clearly visible in the folded light curve. The photometric amplitude that we obtain, K1 = 85.8 km s−1, is ∼12 per cent less than the spectroscopic RV amplitude of 97.2 ± 2.0 km s−1. The discrepancy is due to the photometric contamination from a close object at about 5 arcsec north-west of KIC 6614501, which is difficult to remove. The atmospheric parameters of the sdB star, Teff = 23 700 ± 500 K and log g = 5.70 ± 0.10, imply that it is a rare object below the extreme horizontal branch (EHB), similar to HD 188112. The comparison with different evolutionary tracks suggests a mass between ∼0.18 and ∼0.25 M⊙, too low to sustain core helium burning. If the mass was close to 0.18-0.19 M⊙, the star could be already on the final He-core WD cooling track. A higher mass, up to ∼0.25 M⊙, would be compatible with a He-core WD progenitor undergoing a cooling phase in a H-shell flash loop. A third possibility, with a mass between ∼0.32 and ∼0.40 M⊙, cannot be excluded and would imply that the sdB is a 'normal' (but with an unusually low mass) EHB star burning He in its core. In all these different scenarios, the system is expected to merge in less than 3.1 Gyr due to gravitational wave radiation. [ABSTRACT FROM AUTHOR]

The recently discovered subdwarf B (sdB) pulsator KIC11 558 725 is one of the 16 pulsating sdB stars detected in the Kepler field. It features a rich g-mode frequency spectrum, with a few low-amplitude p-modes at short periods. This makes it a promising target for a seismic study aiming to constrain the internal structure of this star, and of sdB stars in general. We have obtained ground-based spectroscopic radial-velocity measurements of KIC 11 558 725 based on low-resolution spectra in the Balmer-line region, spanning the 2010 and 2011 observing seasons. From these data we have discovered that KIC11 558 725 is a binary with period P = 10.05 d, and that the radial-velocity amplitude of the sdB star is 58 km s-1. Consequently the companion of the sdB star has a minimum mass of 0.63 M☉, and is therefore most likely an unseen white dwarf. We analyse the near-continuous 2010-2011 Kepler light curve to reveal the orbital Doppler-beaming effect, giving rise to light variations at the 238 ppm level, which is consistent with the observed spectroscopic orbital radial-velocity amplitude of the subdwarf. We use the strongest 70 pulsation frequencies in the Kepler light curve of the subdwarf as clocks to derive a third consistent measurement of the orbital radial-velocity amplitude, from the orbital light-travel delay. The orbital radius asdB sin i = 11.5 R☉ gives rise to a light-travel time delay of 53.6 s, which causes aliasing and lowers the amplitudes of the shortest pulsation frequencies, unless the effect is corrected for. We use our high signal-to-noise average spectra to study the atmospheric parameters of the sdB star, deriving Teff = 27 910K and log g = 5.41 dex, and find that carbon, nitrogen and oxygen are underabundant relative to the solar mixture. Furthermore, we analyse the Kepler light curve for its pulsational content and extract more than 160 significant frequencies. We investigate the pulsation frequencies for expected period spacings and rotational splittings. We find period-spacing sequences of spherical-harmonic degrees ɭ = 1 and ɭ = 2, and we associate a large fraction of the g-modes in KIC 11 558 725 with these sequences. From frequency splittings we conclude that the subdwarf is rotating subsynchronously with respect to the orbit. [ABSTRACT FROM AUTHOR]

Context. Most planetary nebulae have bipolar or other non-spherically symmetric shapes. Magnetic fields in the central star may be responsible for this lack of symmetry, but observational studies published to date have reported contradictory results. Aims. We search for correlations between a magnetic field and departures from the spherical geometry of the envelopes of planetary nebulae. Methods. We determine the magnetic fields from spectropolarimetric observations of ten central stars of planetary nebulae. The results of the analysis of the observations of four stars were previously presented and discussed in the literature, while the observations of six stars, plus additional measurements of a star previously observed, are presented here for the first time. Results. All our determinations of magnetic field in the central planetary nebulae are consistent with null results. Our field measurements have a typical error bar of 150-300 G. Previous spurious field detections using data acquired with FORS1 (FOcal Reducer and low dispersion Spectrograph) of the Unit Telescope 1 (UT1) of the Very Large Telescope (VLT) were probably due to the use of different wavelength calibration solutions for frames obtained at different position angles of the retarder waveplate. Conclusions. There is currently no observational evidence of magnetic fields with a strength of the order of hundreds Gauss or higher in the central stars of planetary nebulae. [ABSTRACT FROM AUTHOR]

ABSTRACT We report on extended photometry of two pulsating subdwarf B (sdB) stars in close binaries. For both cases, we use rotational splitting of the pulsation frequencies to show that the sdB component rotates much too slowly to be in synchronous rotation. We use a theory of tidal interaction in binary stars to place limits on the mass ratios that are independent of estimates based on the radial velocity curves. The companions have masses below 0.26 M⊙. The pulsation spectra show the signature of high-overtone g-mode pulsation. One star, KIC 11179657, has a clear sequence of g modes with equal period spacings as well as several periodicities that depart from that trend. KIC 02991403 shows a similar sequence, but has many more modes that do not fit the simple pattern. [ABSTRACT FROM AUTHOR]

Context. Detection of magnetic fields has been reported in several sdO and sdB stars. Recent literature has cast doubts on the reliability of most of these detections. The situation concerning the occurrence and frequency of magnetic fields in hot subdwarfs is at best confused. Aims. We revisit data previously published in the literature, and we present new observations to clarify the question of how common magnetic fields are in subdwarf stars. Methods. We consider a sample of about 40 hot subdwarf stars. About 30 of them have been observed with the FORS1 and FORS2 instruments of the ESO VLT. Results have been published for only about half of the hot subdwarfs observed with FORS. Here we present new FORS1 field measurements for 17 stars, 14 of which have never been observed for magnetic fields before. We also critically review the measurements already published in the literature, and in particular we try to explain why previous papers based on the same FORS1 data have reported contradictory results. Results. All new and re-reduced measurements obtained with FORS1 are shown to be consistent with non-detection of magnetic fields. We explain previous spurious field detections from data obtained with FORS1 as due to a non-optimal method of wavelength calibration. Field detections in other surveys are found to be uncertain or doubtful, and certainly in need of confirmation. Conclusions. There is presently no strong evidence for the occurrence of a magnetic field in any sdB or sdO star, with typical longitudinal field uncertainties of the order of 2-400 G. It appears that globally simple fields of more than about 1 or 2 kG in strength occur in at most a few percent of hot subdwarfs. Further high-precision surveys, both with high-resolution spectropolarimeters and with instruments similar to FORS1 on large telescopes, would be very valuable. [ABSTRACT FROM AUTHOR]

We introduce the Pan-Pacific Planet Search, a survey of 170 metal-rich Southern Hemisphere subgiants using the 3.9 m Anglo-Australian Telescope. We report the first discovery from this program, a giant planet orbiting 7 CMa (HD 47205) with a period of 763 ± 17 days, eccentricity e = 0.14 ± 0.06, and m sin i = 2.6 ± 0.6 Mjup. The host star is a K giant with a mass of 1.5 ± 0.3 M⊙ and metallicity [Fe/H] = 0.21 ± 0.10. The mass and period of 7 CMa b are typical of planets which have been found to orbit intermediate-mass stars (M* > 1.3 M⊙). Hipparcos photometry shows this star to be stable to 0.0004 mag on the radial-velocity period, giving confidence that this signal can be attributed to reflex motion caused by an orbiting planet. [ABSTRACT FROM AUTHOR]

ABSTRACT We have identified a star in the Wide Angle Search for Planets (WASP) archive photometry with an unusual light curve due to the total eclipse of a small, hot star by an apparently normal A-type star and with an orbital period of only 0.668 d. From an analysis of the WASP light curve together with V-band and IC-band photometry of the eclipse and a spectroscopic orbit for the A-type star we estimate that the companion star has a mass of 0.23 ± 0.03 M⊙ and a radius of 0.33 ± 0.01 R⊙, assuming that the A-type star is a main-sequence star with the metallicity appropriate for a thick-disc star. The effective temperature of the companion is 13 400 ± 1200 K from which we infer a luminosity of 3 ± 1 L⊙. From a comparison of these parameters to various models we conclude that the companion is most likely to be the remnant of a red giant star that has been very recently stripped of its outer layers by mass transfer on to the A-type star. In this scenario, the companion is currently in a shell hydrogen-burning phase of its evolution, evolving at nearly constant luminosity to hotter effective temperatures prior to ceasing hydrogen burning and fading to become a low-mass white dwarf composed of helium (He-WD). The system will then resemble the pre-He-WD/He-WD companions to A- and B-type stars recently identified from their Kepler satellite light curves (KOI-74, KOI-81 and KIC 10657664). This newly discovered binary offers the opportunity to study the evolution of a stripped red giant star through the pre-He-WD stage in great detail. [ABSTRACT FROM AUTHOR]

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Background: The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC.Methods: The ER+ tumours were classified as 'luminal A' (LA): ER+ and/or PR+, Ki-67 low, p53-, HER2- or 'luminal B' (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS).Results: In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6-19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555-8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501-6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629-8.031, P=0.002) but not IBTR.Conclusion: The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy. [ABSTRACT FROM AUTHOR]

Background In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti-Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear. Aim The aim of the study was to assess concordance between serum AMH and testosterone concentrations following hCG stimulation of two different durations. Methods Samples from 284 children (M : F, 154 : 130) with a median age of 8 years (10th, 90th centiles, 0·25, 14) were used to establish an AMH reference range. Clinical data were reviewed in boys undergoing investigation of gonadal function and who had an AMH measurement and a hCG stimulated (3-day or 3-week) ( n = 26) testosterone. Of these 26 boys, 11 had combined genital anomalies, whereas the rest had conditions such as isolated hypospadias, undescended testes or microphallus. Normal testosterone response to hCG stimulation was defined as a level greater than 3·5 nmol at day 4 and 9·5 nmol/l at day 22. Results In the reference group, the 5th centile AMH for boys below 1 year was 215 pmol/l and between 1 and 8 years 180 pmol/l. The 95th centile for girls for these respective age groups was 30 pmol/l and 25 pmol/l. In those cases where serum testosterone concentrations were available at day 1, day 4 and day 22 of the 3 week-hCG test, five cases had a normal serum testosterone at day 4 and three cases only showed such a response by day 22. In those where serum AMH was less than 180 pmol/l, a poor testosterone response of less than 3·5 nmol was observed in approximately seven of eight (88%) cases with a 3-day hCG stimulation test or the 3-week test. An AMH of greater than 180 pmol/l was associated with a normal testosterone response at day 4 in 10 out of 15 (67%) cases and at day 22 in eight of 11 (73%) cases. However, a low serum testosterone concentration of less than 3·5 nmol after the 3-day hCG test was only associated with a likelihood of a low AMH in three of eight (37%) cases. With the 3-week hCG test, a low day 22 testosterone of 9·5 mmol/l or less was associated with a low AMH of 180 pmol/l or less in four of seven (57%) cases. Conclusion In boys undergoing investigation of gonadal function, the concordance between AMH and testosterone is better at day 22 than day 4. A normal AMH may provide useful information on overall testicular function but does not exclude the need for an hCG stimulation test. [ABSTRACT FROM AUTHOR]

Aberrant expression of cyclin D1 protein is a common feature of breast cancer. However, the CCND1 gene encodes two gene products, cyclin D1a and cyclin D1b, which have discrete mechanisms of regulation and impact on cell behavior. A polymorphism at nucleotide 870 in the CCND1 gene, rs603965, influences the relative production of the encoded proteins and can impart increased risk for tumor development. Here, the impact of both the G/A870 polymorphism and cyclin D1b protein production on breast cancer risk, disease phenotype and patient outcome was analysed. In a large multiethnic case–control study, the G/A870 polymorphism conferred no significant risk for breast cancer overall or by stage or estrogen receptor (ER) status. However, the cyclin D1b protein was found to be upregulated in breast cancer, independent of cyclin D1a levels, and exhibited heterogeneous levels in breast cancer specimens. High cyclin D1a expression inversely correlated with the Ki67 proliferation marker and was not associated with clinical outcome. In contrast, elevated cyclin D1b expression was independently associated with adverse outcomes, including recurrence, distant metastasis and decreased survival. Interestingly, cyclin D1b was particularly associated with poor outcome in the context of ER-negative breast cancer. Thus, specific cyclin D1 isoforms are associated with discrete forms of breast cancer and high cyclin D1b protein levels hold prognostic potential.Oncogene (2009) 28, 1812–1820; doi:10.1038/onc.2009.13; published online 16 March 2009 [ABSTRACT FROM AUTHOR]