Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis and resistance to therapy. We hypothesised that this aggressive phenotype is because of an ...intrinsically elevated hypoxic response. Microarrayed tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours. Tumour subtypes were correlated with standard clincopathological parameters as well as hypoxic markers. Out of 456 tumours 62 (14%) tumours were basal-like. These tumours were positively correlated with high tumour grade (P<0.001) and were associated with a significantly worse disease-free survival compared with luminal tumours (P<0.001). Fifty percent of basal-like tumours expressed HIF-1alpha, and more than half expressed at least one of the PHD enzymes and FIH-1. Basal-like tumours were nine times more likely to be associated with CAIX expression (P<0.001) in a multivariate analysis. Carbonic anhydrase IX expression was positively correlated with tumour size (P=0.005), tumour grade (P<0.001) and oestrogen receptor (ER) negativity (P<0.001). Patients with any CAIX-positive breast tumour phenotype and in the basal tumour group had a significantly worse prognosis than CAIX-negative tumours when treated with chemotherapy (P<0.001 and P=0.03, respectively). The association between basal phenotype and CAIX suggests that the more aggressive behaviour of these tumours is partly due to an enhanced hypoxic response. Further, the association with chemoresistance in CAIX-positive breast tumours and basal-like tumours in particular raises the possibility that targeted therapy against HIF pathway or downstream genes such as CAs may be an approach to investigate for these patients.
Determining the orbital eccentricity of an extrasolar planet is critically important for understanding the system's dynamical environment and history. However, eccentricity is often poorly determined ...or entirely mischaracterized due to poor observational sampling, low signal-to-noise, and/or degeneracies with other planetary signals. Some systems previously thought to contain a single, moderate-eccentricity planet have been shown, after further monitoring, to host two planets on nearly circular orbits. We investigate published apparent single-planet systems to see if the available data can be better fit by two lower-eccentricity planets. We identify nine promising candidate systems and perform detailed dynamical tests to confirm the stability of the potential new multiple-planet systems. Finally, we compare the expected orbits of the single- and double-planet scenarios to better inform future observations of these interesting systems.
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.
Summary Cognitive-behavioral therapy for insomnia (CBT-I) has been shown efficacious, but the challenge remains to make it available and accessible in order to meet population needs. Delivering CBT-I ...over the internet (eCBT-I) may be one method to overcome this challenge. The objective of this meta-analysis was to evaluate the efficacy of eCBT-I and the moderating influence of various study characteristics. Two researchers independently searched key electronic databases (1991 to June 2015), selected eligible publications, extracted data, and evaluated methodological quality. Eleven randomized controlled trials examining a total of 1460 participants were included. Results showed that eCBT-I improved insomnia severity, sleep efficiency, subjective sleep quality, wake after sleep onset, sleep onset latency, total sleep time, and number of nocturnal awakenings at post-treatment, with effect sizes (Hedges's g ) ranging from 0.21 to 1.09. The effects were comparable to those found for face-to-face CBT-I, and were generally maintained at 4–48 wk follow-up. Moderator analyses showed that longer treatment duration and higher degree of personal clinical support were associated with larger effect sizes, and that larger study dropout in the intervention group was associated with smaller effect sizes. In conclusion, internet-delivered CBT-I appears efficacious and can be considered a viable option in the treatment of insomnia.
We investigate the possibility of nearly equally spaced periods in 13 hot subdwarf B (sdB) stars observed with the Kepler spacecraft and one observed with CoRoT. Asymptotic limits for gravity ...(g-)mode pulsations provide relationships between equal-period spacings of modes with differing degrees ℓ and relationships between periods of the same radial order n but differing degrees ℓ. Period transforms, Kolmogorov-Smirnov tests and linear least-squares fits have been used to detect and determine the significance of equal-period spacings. We have also used Monte Carlo simulations to estimate the likelihood that the detected spacings could be produced randomly.
Period transforms for nine of the Kepler stars indicate ℓ= 1 period spacings, with five also showing peaks for ℓ= 2 modes. 12 stars indicate ℓ= 1 modes using the Kolmogorov-Smirnov test while another shows solely ℓ= 2 modes. Monte Carlo results indicate that equal-period spacings are significant in 10 stars above 99 per cent confidence, and 13 of the 14 are above 94 per cent confidence. For 12 stars, the various methods find consistent period spacings to within the errors, two others show some inconsistencies, likely caused by binarity, and the last has significant detections but the mode assignment disagrees between the methods.
We use asymptotic period spacing relationships to associate observed periods of variability with pulsation modes for ℓ= 1 and 2. From the Kepler first-year survey sample of 13 multiperiodic g-mode pulsators, five stars have several consecutive overtones making period spacings easy to detect, six others have fewer consecutive overtones but period spacings are readily detected, and two stars show marginal indications of equal-period spacings. We also examine a g-mode sdB pulsator observed by CoRoT with a rich pulsation spectrum, and our tests detect regular period spacings.
We use Monte Carlo simulations to estimate the significance of the detections in individual stars. From the simulations, it is determined that regular period spacings in 10 of the 14 stars are very unlikely to be random, another two are moderately unlikely to be random and two are mostly unconstrained.
We find a common ℓ= 1 period spacing spanning a range from 231 to 272 s allowing us to correlate pulsation modes with 222 periodicities and that the ℓ= 2 period spacings are related to the ℓ= 1 spacings by the asymptotic relationship
. We briefly discuss the impact of equal-period spacings which indicate low-degree modes with a lack of significant mode trappings.
We report the discovery of two long-period giant planets from the Anglo-Australian Planet Search. HD 154857c is in a multiple-planet system, while HD 114613b appears to be solitary. HD 114613b has an ...orbital period P = 10.5 yr, and a minimum mass m sin i of 0.48 M sub(Jup); HD 154857c has P = 9.5 yr and m sin i = 2.6 M sub(Jup). These new data confirm the planetary nature of the previously unconstrained long-period object in the HD 154857 system.We have performed detailed dynamical stability simulations which show that the HD 154857 two-planet system is stable on timescales of at least 10 super(8) yr. These results highlight the continued importance of "legacy" surveys with long observational baselines; these ongoing campaigns are critical for determining the population of Jupiter analogs, and hence of those planetary systems with architectures most like our own solar system.
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.
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).
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.
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
Informal caregivers (ICs) are integral to care provided to patients facing life-threatening or incurable illnesses. This responsibility causes considerable burden, as approximately one half ...of ICs report clinically significant symptoms of depression and/or anxiety that persist when left untreated. Psychosocial interventions containing efficacious treatment principles (e.g., cognitive behavior therapy CBT) show disappointing results in reducing anxiety and depression in ICs. This may reflect failure of these interventions to specifically target crucial mechanisms underlying the central feature of distress caused by the patient’s illness—notably, perseverative negative thinking (PNT). Emotion Regulation Therapy (ERT) is an efficacious CBT developed to explicitly target mechanisms underlying PNT and the emotional concomitants that arise in response to stressful situations. This open trial was conducted to evaluate the acceptability and initial efficacy of ERT adapted to the experience of cancer ICs (ERT-C). Thirty-one ICs provided informed consent and completed eight weekly individual sessions of ERT-C. Participants completed self-report measures of depression and anxiety symptoms, PNT, emotion regulation deficits, and caregiver burden before and after treatment. ERT-C was well tolerated as indicated by 22 treatment completers and feedback provided in exit interviews. ICs demonstrated reduced depression and anxiety symptoms, PNT, and emotion regulation deficits with moderate to large effect sizes (Hedge’s g range: 0.36–0.92). Notably, caregiver burden was not reduced but ICs expressed more ability to confront caregiving-related challenges. Findings offer promising but preliminary support for ERT-C as a conceptual model and treatment modality for distressed cancer ICs.
Emotion Regulation Therapy (ERT) was well tolerated and demonstrated reduced depression, anxiety, perseverative negative thinking, and emotion regulation deficits in distressed cancer caregivers.
Highlights ► Social anxiety is associated with reduced emotion knowledge. ► Patients with social anxiety disorder show very poor intrapersonal emotion knowledge. ► No differences on emotion knowledge ...between anxiety disorders were detected.
This article systematically reviews studies investigating the effect of three operationalizations of complexity in emotion experience (i.e., differentiation, covariation, and variability) on ...situational behavioral adaptation (i.e., physiological, cognitive, and overt action responses), and quantifies the results with meta-analyses. Twenty-seven studies of emotion complexity were identified and divided into four categories: (a) trait and (b) state studies within clinical samples, and (c) trait and (d) state studies within nonclinical samples. Most studies investigated trait emotion differentiation, revealing negligible to small effects (r range: .06 to .15). Only 4 studies in total assessed indicators of state emotion complexity. The theoretical assumptions behind the indicators of emotion complexity as well as the conceptualization of behavioral adaptiveness are critically discussed, and a number of future avenues for this type of research are proposed.
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