Lense-Thirring precession after a supermassive black hole disrupts a star.

An accretion disk formed around a supermassive black hole after it disrupts a star is expected to be initially misaligned with respect to the equatorial plane of the black hole. This misalignment induces relativistic torques (the Lense-Thirring effect) on the disk, causing the disk to precess at early times, whereas at late times the disk aligns with the black hole and precession terminates1,2. Here we report, using high-cadence X-ray monitoring observations of a tidal disruption event (TDE), the discovery of strong, quasi-periodic X-ray flux and temperature modulations. These X-ray modulations are separated by roughly 15 days and persist for about 130 days during the early phase of the TDE. Lense-Thirring precession of the accretion flow can produce this X-ray variability, but other physical mechanisms, such as the radiation-pressure instability3,4, cannot be ruled out. Assuming typical TDE parameters, that is, a solar-like star with the resulting disk extending at most to the so-called circularization radius, and that the disk precesses as a rigid body, we constrain the disrupting dimensionless spin parameter of the black hole to be 0.05 ≲ ∣a∣ ≲ 0.5.

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2-/- Vav3-/- Tiam1-/-), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.

Seasonal evolution of Titan's stratosphere during the Cassini mission.

Titan's stratosphere exhibits significant seasonal changes, including break-up and formation of polar vortices. Here we present the first analysis of mid-infrared mapping observations from Cassini's Composite InfraRed Spectrometer (CIRS) to cover the entire mission (Ls=293-93°, 2004-2017) - mid-northern winter to northern summer solstice. The north-polar winter vortex persisted well after equinox, starting break-up around Ls∼60°, and fully dissipating by Ls∼90°. Absence of enriched polar air spreading to lower latitudes suggests large-scale circulation changes and photochemistry control chemical evolution during vortex break-up. South-polar vortex formation commenced soon after equinox and by Ls∼60° was more enriched in trace gases than the northern mid-winter vortex and had temperatures ∼20 K colder. This suggests early-winter and mid-winter vortices are dominated by different processes - radiative cooling and subsidence-induced adiabatic heating respectively. By the end of the mission (Ls=93°) south-polar conditions were approaching those observed in the north at Ls=293°, implying seasonal symmetry in Titan's vortices.

Less absorbed solar energy and more internal heat for Jupiter.

The radiant energy budget and internal heat are fundamental properties of giant planets, but precise determination of these properties remains a challenge. Here, we report measurements of Jupiter's radiant energy budget and internal heat based on Cassini multi-instrument observations. Our findings reveal that Jupiter's Bond albedo and internal heat, 0.503 ± 0.012 and 7.485 ± 0.160 W m-2 respectively, are significantly larger than 0.343 ± 0.032 and 5.444 ± 0.425 Wm-2, the previous best estimates. The new results help constrain and improve the current evolutionary theories and models for Jupiter. Furthermore, the significant wavelength dependency of Jupiter's albedo implies that the radiant energy budgets and internal heat of the other giant planets in our solar system should be re-examined. Finally, the data sets of Jupiter's characteristics of reflective solar spectral irradiance provide an observational basis for the models of giant exoplanets.

Wnt ligands influence tumour initiation by controlling the number of intestinal stem cells.

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.

SEASONAL EVOLUTION OF TITAN'S STRATOSPHERE NEAR THE POLES.

In this paper we report the monitoring of seasonal evolution near Titan's poles. We find Titan's south pole to exhibit since 2010 a strong temperature decrease and a dramatic enhancement of several trace species such as complex hydrocarbons and nitriles (HC3N and C6H6 in particular) previously only observed at high northern latitudes (Coustenis et al. 2016 and references therein). This results from the seasonal change on Titan going from winter (2002) to summer (2017) in the north and, at the same time, the onset of winter in the south pole. During this transition period atmospheric components with longer chemical lifetimes linger in the north undergoing slow photochemical destruction, while those with shorter lifetimes decrease and reappear in the south. An opposite effect was expected in the north, but not observed with certainty until now. We present here an analysis of high-resolution nadir spectra acquired by Cassini/CIRS at in the past years and describe the temperature and composition variations near Titan's poles. From 2013 until 2016, the northern polar region has shown a temperature increase of 10 K, while the south has shown a more significant decrease (up to 25 K) in a similar period of time. While the south polar region is continuously enhanced since about 2012, the chemical content in the north is finally showing a clear depletion for most molecules only since 2015. This is indicative of a non-symmetrical response to the seasons in Titan's stratosphere that can set constraints on photochemical and GCM models.

Composite infrared spectrometer (CIRS) on Cassini.

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

Composite infrared spectrometer (CIRS) on Cassini: publisher's note.

This publisher's note renumbers the reference list in Appl. Opt.56, 5274 (2017)APOPAI0003-693510.1364/AO.56.005274.

Measuring patient activation: The utility of the Patient Activation Measure within a UK context-Results from four exemplar studies and potential future applications.

OBJECTIVE: Patient activation can be measured using the Patient Activation Measure (PAM) developed by Hibbard et al., however, little is known about the uses of the PAM in research and in practice. This study aims to explore its differing utility in four UK exemplar sites. METHODS: Data from four exemplars in a range of health settings with people living with long-term conditions (i.e. stroke or COPD) were evaluated. PAM scores were described and explored in relation to clinical and sociodemographic variables and outcome measures. RESULTS: PAM scores illustrated that most with COPD or stroke reported PAM levels of 3 or 4, indicating that they are engaging, but may need help to sustain their scores. The exemplars illustrate the utility of, and potential issues involved in, using PAM as a process/outcome measure to predict activation and the effectiveness of interventions, and as a tool to inform tailoring of targeted interventions. CONCLUSIONS: The PAM tool has been shown to be useful as an outcome measure, a screening tool to tailor education, or a quality indicator for delivery of care. PRACTICE IMPLICATIONS: However good demographic and patient history are needed to substantiate PAM scores. Further work is needed to monitor PAM prospectively.

Electromagnetic needle tracking during simulated right internal jugular cannulation.

This study used three-dimensional information from Stealth navigation technology during simulated right internal jugular vein cannulation to define the initial needle trajectory taken when using three approaches: landmark (LM), short-axis (SAX) ultrasound and long-axis (LAX) ultrasound. Nineteen volunteers indicated the entry site and needle direction (track) they would use in performing right internal jugular vein cannulation by the three approaches. The likelihood of cannulation success, arterial puncture and needle direction were recorded. Volunteers were asked to assess the suitability of the simulation system for validity and educational benefit. The SAX track crossed the jugular vein more frequently than the LAX and LM tracks (SAX: 94%; LAX: 80%; LM: 47% [SAX versus LM, P <0.01]). The mean indicated needle direction in the coronal plane for LM, SAX and LAX were -4, 13 and 11 degrees, respectively. The track associated with the LAX technique would have entered the carotid artery by 16% of volunteers. At needle depths of over 40 mm, the track crossed the vertebral artery at the following rates (LM: 11%; SAX: 16%; LAX: 16%). The use of Stealth technology to provide three-dimensional feedback of the needle path taken during simulated right internal jugular cannulation was considered realistic (16/19) and of benefit for 18 of 19 (95%) respondents. The SAX track was associated with the highest likelihood of successful jugular cannulation and the lowest cross rate of the carotid artery. The simulation model using Stealth was considered to be valuable and realistic by participants despite some limitations.

E2F1 drives chemotherapeutic drug resistance via ABCG2.

Multidrug resistance is a major barrier against successful chemotherapy, and this has been shown in vitro to be often caused by ATP-binding cassette (ABC) transporters. These transporters are frequently overexpressed in human cancers and confer an adverse prognosis in many common malignancies. The genetic factors, however, that initiate their expression in cancer are largely unknown. Here we report that the major multidrug transporter ABCG2 (BCRP/MXR) is directly and specifically activated by the transcription factor E2F1--a factor perturbed in the majority of human cancers. E2F1 regulates ABCG2 expression in multiple cell systems, and, importantly, we have identified a significant correlation between elevated E2F1 and ABCG2 expression in human lung cancers. We show that E2F1 causes chemotherapeutic drug efflux both in vitro and in vivo via ABCG2. Furthermore, the E2F1-ABCG2 axis suppresses chemotherapy-induced cell death that can be restored by the inhibition of ABCG2. These findings therefore identify a new axis in multidrug resistance and highlight a radical new function of E2F1 that is relevant to tumor therapy.

Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion.

Tumour-derived mutant p53 proteins promote invasion, in part, by enhancing Rab coupling protein (RCP)-dependent receptor recycling. Here we identified MET as an RCP-binding protein and showed that mutant p53 promoted MET recycling. Mutant p53-expressing cells were more sensitive to hepatocyte growth factor, the ligand for MET, leading to enhanced MET signalling, invasion and cell scattering that was dependent on both MET and RCP. In cells expressing the p53 family member TAp63, inhibition of TAp63 also lead to cell scattering and MET-dependent invasion. However, in cells that express very low levels of TAp63, the ability of mutant p53 to promote MET-dependent cell scattering was independent of TAp63. Taken together, our data show that mutant p53 can enhance MET signalling to promote cell scattering and invasion through both TAp63-dependent and -independent mechanisms. MET has a predominant role in metastatic progression and the identification of mechanisms through which mutations in p53 can drive MET signalling may help to identify and direct therapy.

A narrative review of psychological and educational strategies applied to young children's eating behaviours aimed at reducing obesity risk.

Strategies to reduce risk of obesity by influencing preschool children's eating behaviour are reviewed. The studies are placed in the context of relevant psychological processes, including inherited and acquired preferences, and behavioural traits, such as food neophobia, 'enjoyment of food' and 'satiety responsiveness'. These are important influences on how children respond to feeding practices, as well as predictors of obesity risk. Nevertheless, in young children, food environment and experience are especially important for establishing eating habits and food preferences. Providing information to parents, or to children, on healthy feeding is insufficient. Acceptance of healthy foods can be encouraged by five to ten repeated tastes. Recent evidence suggests rewarding healthy eating can be successful, even for verbal praise alone, but that palatable foods should not be used as rewards for eating. Intake of healthier foods can be promoted by increasing portion size, especially in the beginning of the meal. Parental strategies of pressuring to eat and restriction do not appear to be causally linked to obesity, but are instead primarily responses to children's eating tendencies and weight. Moderate rather than frequent restriction may improve healthy eating in children. Actively positive social modelling by adults and peers can be effective in encouraging healthier eating.

Critical narrative review to identify educational strategies promoting physical activity in preschool.

The aim of this narrative review is critically to evaluate educational strategies promoting physical activity that are used in the preschool setting in the context of obesity prevention programmes. Literature search was conducted between April and August 2010 in English and German databases (PubMED, PsychINFO, PSYNDEX, ERIC, FIS Bildung). Outcomes considered were time and intensity of physical activity, motor skills or measures of body composition. A total of 19 studies were included. Ten studies added physical activity lessons into their curriculum, one study provided more time for free play, eight studies focused on the social and play environment. Studies reporting positive outcomes implemented physical activity sessions that lasted at least 30 min d(-1). Several studies showed that children are most active in the first 10-15 min. The existence or installation of playground markings or fixed play equipment had no effect, whereas the presence or addition of portable play equipment was positively correlated with moderate-to-vigorous physical activity. Teacher training may be a key element for successful interventions. To overcome time constraints, a suggested solution is to integrate physical activity into daily routines and other areas of the preschool curriculum.

Identifying effective behavioural models and behaviour change strategies underpinning preschool- and school-based obesity prevention interventions aimed at 4-6-year-olds: a systematic review.

The aim of this comprehensive systematic review was to identify the most effective behavioural models and behaviour change strategies, underpinning preschool- and school-based interventions aimed at preventing obesity in 4-6-year-olds. Searching was conducted from April 1995 to April 2010 using MEDLINE, EMBASE, CINAHL, PsycINFO and The Cochrane Library. Epidemiological studies relevant to the research question with controlled assignment of participants were included in the review, if they had follow-up periods of 6 months or longer. Outcomes included markers of weight gain; markers of body composition; physical activity behaviour changes and dietary behaviour changes. Twelve studies were included in the review. The most commonly used model was social cognitive theory (SCT)/social learning theory (SLT) either as a single model or in combination with other behavioural models. Studies that used SCT/SLT in the development of the intervention had significant favourable changes in one, or more, outcome measures. In addition, interventions that (i) combined high levels of parental involvement and interactive school-based learning; (ii) targeted physical activity and dietary change; and (iii) included long-term follow-up, appeared most effective. It is suggested that interventions should also be focused on developing children's (and parents') perceived competence at making dietary and physical changes.

Evidence-based recommendations for the development of obesity prevention programs targeted at preschool children.

The ToyBox intervention was developed using an evidence-based approach, using the findings of four reviews. These reviews included three critical and narrative reviews of educational strategies and psychological approaches explaining young children's acquisition and formation of energy-balance related behaviours, and the management of these behaviours, and also a systematic review of behavioural models underpinning school-based interventions in preschool and school settings for the prevention of obesity in children aged 4-6 years. This paper summarises and translates the findings from these reviews into practical evidence based recommendations for researchers and policy-makers to consider when developing and implementing interventions for the prevention of overweight and obesity in young (aged 4-6 years) children. The recommendations focus on two behaviours, physical activity and sedentary behaviour, and healthy eating, and include general recommendations, intervention approaches, interventions content, and simple messages. The review also briefly examines the role that the commercial sector plays in hindering or facilitating attempts to create healthy food environments for children. This paper also recognises that childhood obesity is not an issue for the education sector alone; it needs to be tackled at a multi sectoral level, recognizing the particularly important role of local governments, nongovernment organizations and the media.

ERK5 signalling in prostate cancer promotes an invasive phenotype.

BACKGROUND: Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)-extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (PCa). The molecular basis of ERK5-driven carcinogenesis and its clinical relevance remain to be fully characterised. METHODS: Modulation of ERK5 expression or function in human PCa PC3 and PC3-ERK5 (stably transfected with ERK5) cells was performed using siRNA-mediated knockdown or the MEK inhibitor PD18435 respectively. In vitro significance of ERK5 signalling was assessed by assays for proliferation, motility, invasion and invadopodia. Expression of matrix metalloproteinases/tissue inhibitors of metalloproteases was determined by Q-RT-PCR. Extracellular signal-regulated protein kinase 5 expression in primary and metastatic PCa was examined using immunohistochemistry. RESULTS: Reduction of ERK5 expression or signalling significantly inhibited the motility and invasive capability of PC3 cells. Extracellular signal-regulated protein kinase 5-mediated signalling significantly promoted formation of in vivo metastasis in an orthotopic PCa model (P<0.05). Invadopodia formation was also enhanced by forced ERK5 expression in PC3 cells. Furthermore, in metastatic PCa, nuclear ERK5 immunoreactivity was significantly upregulated when compared with benign prostatic hyperplasia and primary PCa (P=0.013 and P<0.0001, respectively). CONCLUSION: Our in vitro, in vivo and clinical data support an important role for the MEK5-ERK5 signalling pathway in invasive PCa, which represents a potential target for therapy in primary and metastatic PCa.

Trinidadian women's knowledge, perceptions, and preferences regarding cesarean section: How do they make choices?

OBJECTIVES: The objective of this study is to determine the awareness of perception and attitude toward cesarean section (CS) in a high-user setting. DESIGN AND METHODS: A cross-sectional design using multistage sampling methods was used to select participants from antenatal and postnatal clinics in a primary health care setting in north Trinidad. A multi-item structured questionnaire was designed and administered by in-depth interviews. Sociodemographic data and data about history of previous pregnancies and outcomes and about knowledge and perceptions of CSs were collected from women aged 16 years and older. RESULTS: Of the women who were eligible for entry into the study, 368 participated. However, participants chose not to respond to some questions. The majority of women (46.2%) were found to have very little information from which to make informed decisions about selecting CS as the preferred choice of delivery. Their preference was significantly associated with the perception of safety (maternal or fetal death, P = 0.001), difficulty (complications to mother and baby, P = 0.001), and pain (P = 0.001). Notwithstanding, persons who received information from health care professionals (odds ratio [OR], 1.9; confidence interval, 1.50-2.33) were more likely to have high or adequate levels of information about CSs. Data were analyzed using SPSS software, and ORs were calculated using logistic regression. CONCLUSION: The majority of women attending antenatal and postnatal clinics in north Trinidad were not sufficiently knowledgeable about CS to enable them to make informed choices. In addition, the information obtained was from an unreliable source, emphasizing the need for information on CS to form a component of a structured antenatal education program.

Anaemia in pregnancy: associations with parity, abortions and child spacing in primary healthcare clinic attendees in Trinidad and Tobago.

OBJECTIVE: To determine the prevalence of anaemia in antenatal clinic attendees; to investigate the effects of parity, age, gravidity, previous abortions, child spacing and other factors on the prevalence of anaemia in pregnancy. METHODS: This was a retrospective and cross-sectional study. Antenatal records of 2287 pregnant women attending 40 public healthcare centres from January 2000 to December 2005 in Trinidad and Tobago were used. Data pertaining to the investigated variables were recorded. The national prevalence of anaemia was calculated and chi-square tests, odds ratios and logistic regression were used to assess the relationship between anaemia and each variable. RESULTS: The prevalence of anaemia was 15.3% (95% CI 13.4%, 16.6%). No significant difference in the prevalence of anaemia was found among the different clinics or counties. At the first haemoglobin reading, age was inversely related to the presence of anaemia, whereas gestational age at first visit was directly related. At the final haemoglobin reading, parity, gravidity, and previous spontaneous abortions were directly related to the prevalence of anaemia, while the number of visits was inversely related. Age was inversely associated to the severity of anaemia while gravidity was directly related. CONCLUSION: The prevalence of anaemia decreased by 18.7% from 1967. Despite this positive indication, women under 24 years and those commencing antenatal care after the first trimester are still at a higher risk for developing anaemia. Early commencement of antenatal care and close monitoring of the risk groups identified should be strongly advocated.

Mapping Titan's HCN in the far infra-red: implications for photochemistry.

Observations of Titan's far infra-red spectra by the Cassini orbiter's Composite InfraRed Spectrometer have been used to determine the latitude distribution of HCN at 1 mbar by fitting the HCN and CO rotational lines in the 18-60 cm(-1) (160-550 microm) spectral range. Results confirm the north polar HCN enrichment previously observed using mid-IR data and support the conclusion that Titan's nitrile species are significantly more enriched than hydrocarbons species with similar predicted photochemical lifetimes. This suggests Titan's photochemical cycle includes an additional sink for nitrogen bearing species. The abundance of CO was also determined, and had a mean value of 55 +/- 6 ppm at 20 mbar. However, it was not possible to reliably determine the CO latitude variation due to unconstrained temperatures in the north polar lower stratosphere.