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Erdafitinib in Patients with High- and Intermediate-risk Non–muscle-invasive Bladder Cancer: Final Analysis of THOR-2 Study
Get PDFBackground and objective: High-risk (HR) or intermediate-risk (IR) non–muscle-invasive bladder cancer (NMIBC) carries a high probability of recurrence and/or progression. We present the final analysis results of erdafitinib in HR- or IR-NMIBC with fibroblast growth factor receptor 3/2 alterations (FGFR3/2alt) from the phase 2 THOR-2 study. Methods: Cohort 1 (HR-NMIBC papillary only) with prior bacillus Calmette-Guérin was randomized 2:1 to erdafitinib or intravesical chemotherapy. Cohorts 2 (carcinoma in situ ± papillary) and 3 (IR-NMIBC) received erdafitinib. The primary endpoint was recurrence-free survival (RFS) for cohort 1. Exploratory endpoints included complete response (CR) rate and duration of response (DoR) for cohorts 2 and 3. Key findings and limitations: In cohort 1 (n = 73), median RFS was not reached (NR) for erdafitinib (95% confidence interval [CI] 28.6 mo–not estimable [NE]) and 11.6 mo (95% CI 5.3–NE) for intravesical chemotherapy (hazard ratio 0.28 [95% CI 0.13–0.61; nominal p = 0.0007]; median follow-up, 18.5 and 16.6 mo, respectively). In cohort 2 (n = 16), CR rates were 94% (95% CI 70–100%) and 81% (95% CI 54–96%) at 8 and 32 wk, respectively; the median DoR (mDoR) was 23.3 mo (95% CI 10.0–NE; n = 15). In cohort 3 (n = 18), the CR rate was 89% (95% CI 65–99%) and mDoR was NR (95% CI 13.4 mo–NE). Most common treatment-related adverse event in pooled erdafitinib cohorts (N = 83) was hyperphosphatemia (76%). Limitations include early termination in cohort 1 and small sample size that precluded prespecified hypothesis testing. Conclusions and clinical implications: Oral erdafitinib demonstrated high efficacy in FGFR3/2alt HR-/IR-NMIBC, with a manageable safety profile
‘Reforesting’ environmental education: a philosophical and praxiological reflection from practitioner-researchers in higher education
Get PDFThis paper presents a philosophical and praxiological enquiry into a flagship MSc programme in Outdoor and Environmental Education in the UK that emphasises co-creation of knowledge and reflexive practice among students and academic staff. Using a trioethnographic approach, it brings together critical reflections from three researcher-practitioners to examine the programme’s philosophical foundations and consider whether and how its curriculum fulfils the aims it espouses, particularly in relation to climate, social and ecological justice. Drawing on critical and wild pedagogies, and informed by Indigenous movements in environmental education, the paper engages with contemporary educational philosophy to propose the concept of ‘reforesting’. Building on Arendt’s notion of natality, ‘reforesting’ is presented as a way of reimagining new beginnings through critical reflection and collective praxis in higher education. In doing so, the paper contributes to discussions about how education might respond to the climate crisis while sustaining an ethos of hope and solidarity
Galaxy interactions in void substructures : Morphology and stellar populations of two triplets from CAVITY
Get PDFContext. Cosmic voids are underdense regions of the Universe that provide a unique environment to study galaxy evolution in relative isolation. Galaxy triplets in voids are rare systems where local interactions may strongly influence galaxy properties. Aims. We study the stellar populations, morphologies, mass assembly histories, and dynamical properties of six galaxies belonging to two void triplets from the Calar Alto Void Integral-field Treasury surveY (CAVITY): CAVITY5273X and VGS31. Methods. We used integral-field unit spectroscopy and performed full spectral fitting with the FADO code, which models stellar and nebular emission simultaneously. Spatially resolved maps of stellar age, metallicity, and star formation rate were reconstructed using the integrated nested Laplace approximation. Morphological properties were derived using morfometryka, emission-line diagnostics were applied, and mass assembly functions were computed. Stellar masses and metallicities were compared to the mass-metallicity relation for void galaxies. Results. The two triplets show different evolutionary behaviours. CAVITY52731 is a massive quenched galaxy hosting an active galactic nucleus, while its companions and all galaxies in VGS31 are dominated by young stellar populations and recent star formation. Five galaxies experienced rapid stellar mass growth in the last 2 Gyr. Disturbed morphologies, including asymmetries and tidal features, indicate ongoing interactions. Galaxies in CAVITY5273X follow the expected void mass-metallicity relation, while VGS31 members show significant deviations. Conclusions. Our results show that local interactions can drive significant galaxy evolution even in the most underdense cosmic environments
Lord of LRDs: insights into a 'Little Red Dot' with a low-ionization spectrum at z = 0.1
Get PDFRecent observations by the James Webb Space Telescope (JWST) have revealed a puzzling population of optically red and compact galaxies with peculiar ‘V’-shaped spectra at high redshift, known as ‘Little Red Dots’ (LRDs). Until now, most spectroscopically confirmed LRDs are found at and it has been speculated that LRDs are tracing the early stages of black hole evolution. We report an independent rediscovery of a broad-line active galactic nucleus (AGN), SDSS J102530.29+140207.3, at , which shows spectral features matching those of LRDs seen in the early Universe, including the V-shaped spectrum, broad Balmer lines (with widths of 1000–2000 ), and deep Balmer absorption. We present a new GTC observation of this LRD, which reveals an optical continuum similar to those of G-to-K giant stars including an unambiguous G-band absorption originating from the CH molecule. In addition, this local LRD shows a series of absorption lines potentially related to low-ionization ions or atoms but are deeper than what is observed in empirical stellar templates. We further identify a series of [Fe ii] emission lines indicative of low-ionization gas, which we find also present in a JWST-selected LRD at . We find small but statistically significant variability in the H of SDSS J102530.29+140207.3 consistent with previous findings. Finally, we report new observations with NuSTAR. We confirm the extreme X-ray weakness of this LRD, which might imply Compton-thick gas obscuration with . All evidence suggests SDSS J102530.29+140207.3 has a complex gaseous environment and the strong ionic, atomic, and molecular absorptions are hard to explain with typical stellar and AGN models
Finite Element Analysis of Multiaxial Fatigue and Mixed-Mode Crack Growth in Inconel 600
Get PDFThis study investigates the fatigue life prediction of Inconel 600 under multiaxial loading conditions as well as fatigue crack growth under mixed mode (I and II). Finite element simulations based on critical plane criteria were performed for fatigue analysis under combined tensile and shear loading in different non-proportional modes (i.e., phase difference between tensile and shear loads). To achieve this, fully reversed tensile stress with a maximum value of 480 MPa (mean stress: zero) was considered. Subsequently, a constant shear stress of 28 MPa was applied at different phase angles ranging from 0° to 90° in 10-degree intervals (i.e., 0°≤θ≤90°,∆θ=10° ). For all modes, hysteresis stress diagrams were extracted to investigate the cyclic behavior of the material. Furthermore, various fatigue damage models, including Fatemi-Socie, SWT, normal strain, and shear strain, were employed to assess the fatigue life of the samples under different loading modes using MSC software. The results showed that the Fatemi-Socie and shear strain criteria predict the shortest fatigue life for phase difference in the ranges of 0°-30° and 40°-90°, respectively. Therefore, selecting a more conservative criterion is not feasible as it depends on the loading conditions. Additionally, it was found that the most critical conditions occurred at phase difference of 50° and 60°. Next, in order to numerically investigate the crack growth behavior, a semi-Arcan fixture model was used. Simulations were performed for four different loading modes (i.e., fixture settings), considering variations in the loading angle with respect to the longitudinal axis of the crack (0°, 30°, 60°, and 90°). Eventually, crack length graphs were extracted in terms of loading cycles. The results indicated that the lowest and highest crack growth rates occurred when the angle between loading and the longitudinal axis of the crack was 0° and 90°, respectively
An Energy Efficient Relay Selection Algorithm for Clustered Wireless Sensor Networks
Get PDFIn this paper we propose an energy-efficient relayselection algorithm for clustered Wireless Sensor Networks(WSNs). In contrast to conventional multi-hop transmissionschemes adopted in clustered WSNs, where only cluster heads(CHs) participate in the transmission, in our method the relay isselected from a set of candidate nodes within the sourcetransmission range, subject to predefined desired transmissionpower at the source and the relay. The fundamental of thismethod is to forward the source signal using the node whichminimizes the end-to-end total path distance, such that the totalenergy cost per bit is reduced at the relay and at the source.Thus, the node that satisfies the signal-to-noise ratio (SNR)distance-based threshold of both links participates in thetransmission. Taking into consideration the circuit energy cost,the modulation strategy and its impact on energy cost areinvestigated and the optimal choice of the number of bits persymbol is considered to optimize the total energy cost pertransmission. The proposed method is shown to be more energyefficient compared to the traditional multi-hop transmissionand random relay selection in terms of energy cost for a targetbit error rate at the destination. Additionally, the proposedmethod also outperforms both methods in terms of the networklifetime
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No full textGenerating Models of Attentional Cueing and Inhibition of Return With Genetic Programming
Get PDFThe cueing task is a robust experimental paradigm for investigating attention. A centrally presented valid cue, correctly indicating the location of an upcoming target stimulus, leads to quicker responses than an invalid cue. A feature of this paradigm is that increasing the delay between a peripheral cue and a target reverses this effect, where responses become slower for a valid cue, a phenomenon termed inhibition of return (IOR). Using GEMS, a system that utilises genetic programming techniques, we generated potential strategies underlying the facilitation and IOR effects in the cueing paradigm. Models were generated for three experiments differing in their experimental designs, all with good fit to behavioural data. Our approach helps address current issues in the field of attention regarding how it is defined and what mechanisms underlie it. Additional benefits and limitations of this method are discussed
Sleep Inadequacy and the Relationship with Mucosal Immunity and Upper Respiratory Symptoms in Elite Swimmers: A Longitudinal Study Leading into the Commonwealth Games
No full textA total of 23 elite swimmers were recruited between 21/08/2017 and 31/09/2017; however, nine did not complete the eight-month observation due to retiring during the study (n = 4) or because they did not train on the chosen analysis day due to university commitments (n = 5). Therefore, 14 elite national and international swimmers were included. Swimmers were within two training groups: sprint (43%) and middle-distance/distance (57%). A total of 10 swim sessions a week were programmed: five early morning sessions and five afternoon/evening sessions (plus S&C sessions). Prior to study commencement, swimmers provided written fully informed consent and health screens. Ethical approval was granted for human investigation by The University of Hertfordshire, Health Science Engineering & Technology ECDA (Ethics protocol number: aLMS/PGR/UH/02940(1,2,3)). Patients and the public were not involved in design, conduct or reporting of this research, in any way.
Self-reported sleep data was obtained alongside URS data weekly using an adaption of the Australian Institute of Sport (AIS) monthly illness log. Self-perceived sleep quality was monitored by ranking on a scale of 1-10 (1 = poor, 10 = excellent) each week. Moreover, swimmers were asked how many times they thought they had met the NR of 7-9 hours and how many times they had awoken feeling fatigued each week. This sleep data was compared to relative salivary IgA (normalised to each individual's healthy mean), URS, and coach derived training loads of which the methodology has been previously defined[21]. To assess sleep-wake patterns, a wrist-worn activity monitor GT3X+ (ActiGraph, Florida, USA) was worn around the non-dominant wrist during night-time sleep and napping periods only. This was removed when swimmers arose from bed in the morning, or after napping, and swimmers completed daily sleep diaries, which were used to assist in identifying bedtime and wake time for later analysis. Parameters recorded included latency (mins), sleep efficiency (SE; %), total time in bed (TTIB; min), total sleep time (TST; min), wake after sleep onset (WASO; min), number of awakenings, and average time awake (min). Actigraphy data was used to determine objective sleep-wake patterns for different training intensity periods (low, moderate, high training loads and into competition). Actigraphy data was processed using ActiLife software (version 6.13) and individual sleep data reports created by this software were provided to swimmers at the cessation of the study
"We Have a Long Way to Go" : Palliative Care Clinicians' Reflections on Inclusive care for LGBTQI+ Older Adult Patients and Care Partners
No full textBACKGROUND AND OBJECTIVES: Prior research with older lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) populations indicates a need for greater documentation of palliative care clinicians' perspectives on communication and clinician knowledge about these patients' needs. LGBTQI+ patients report barriers to their disclosure of sexual orientation and gender identity data, dismissal of chosen care partners, and personal experiences of discrimination in palliative care. RESEARCH DESIGN AND METHODS: Queer gerontology was applied in this qualitative descriptive study. One-on-one interviews were transcribed, coded, and analyzed using reflexive thematic analysis. Twenty clinicians and associated health care professionals with palliative care training who currently or within the past 5 years had provided care and/or treatment for older LGBTQI+ patients living with serious illness within Colorado participated in this study. RESULTS: Three main themes emerged: (1) limited visibility of LGBTQI+ patients, (2) asking about sexual orientation and gender identity, and (3) acknowledging limitations around the current state of care for LGBTQI+ patients and care partners. DISCUSSION AND IMPLICATIONS: Clinical environments must be inclusive and welcoming to promote a safe space for lesbian, gay, bisexual, transgender, queer, and intersex patients and care partners. Avoiding assumptions around these patients having the same or similar experiences to cisgender, heterosexual patients is critical to making meaningful connections. There is a significant need for lesbian, gay, bisexual, transgender, queer, and intersex-specific culturally relevant training. We recommend improvements in communication, inclusivity, and training/education. Findings indicate several areas to improve trust, equity, and inclusivity