Local administration of irinotecan using an implantable drug delivery device stops high-grade glioma tumor recurrence in a glioblastoma tumor model

The treatment for Glioblastoma is limited due to the presence of the blood brain barrier, which restricts the entry of chemotherapeutic drugs into the brain. Local delivery into the tumor resection margin has the potential to improve efficacy of chemotherapy. We developed a safe and clinically translatable irinotecan implant for local delivery to increase its efficacy while minimizing systemic side effects. Irinotecan-loaded implants were manufactured using hot melt extrusion, gamma sterilized at 25 kGy, and characterized for their irinotecan content, release, and drug diffusion. Their therapeutic efficacy was evaluated in a patient-derived xenograft mouse resection model of glioblastoma. Their safety and translatability were evaluated using histological analysis of brain tissue and serum chemistry analysis. Implants containing 30% and 40% w/w irinotecan were manufactured without plasticizer. The 30% and 40% implants showed moderate local toxicity up to 2- and 6-day post-implantation. Histopathology of the implantation site showed signs of necrosis at days 45 and 14 for the 30% and 40% implants. Hematological analysis and clinical chemistry showed no signs of serious systemic toxicity for either implant. The 30% implants had an 80% survival at day 148, with no sign of tumor recurrence. Gamma sterilization and 12-month storage had no impact on the integrity of the 30% implants. This study demonstrates that the 30% implants are a promising novel treatment for glioblastoma that could be quickly translated into the clinic.</p

Influence of Acute Exercise on Postprandial Lipemia and Fat Oxidation in Active Cannabis Users

Adults residing in industrialized nations spend most of their day in a postprandial state. This can cause prolonged elevated levels of triglycerides and glucose post-meal, leading to increased risk of cardiovascular and metabolic disease. In epidemiological literature, cannabis users have been reported to have similar or lower levels of blood lipids compared to nonusers. However, postprandial responses and whether prior exercise improves postprandial lipemia (PPL) in this population is not known. PURPOSE: To examine the influence of prior exercise on PPL in active cannabis users. METHODS: This analysis presents preliminary data from a larger ongoing study comparing prior exercise and PPL in cannabis users and non-users. Seven active cannabis users (Age: 30 ± 7 years; BMI: 24.3 ± 3.4 kg/m2; VO2max: 47.5 ± 10.8 mL/kg/min) completed 1 hour of exercise at their ventilatory threshold (VT) the evening before a high-fat, high-sugar liquid meal containing 15 kcal/kg body mass. Substrate oxidation, blood pressure, and capillary blood samples were obtained before and every 30-60 minutes post-meal for 3 hours. Blood samples were analyzed for glucose and triglycerides. Repeated-measures ANOVAs were utilized to examine differences in variables between conditions, across time, and their interaction. Area-under-the-curve (AUC) for glucose and triglycerides were calculated by the trapezoidal rule. RESULTS: Participants exercised at an intensity of 96 ± 5% VT (73 ± 11% VO2max) and expended 790 ± 168 kcals with an average RER of 0.92 ± 0.03. Post meal (1141 ± 200 kcals), all variables had significant effects of time (p \u3c 0.05), but no significant effect of condition (Control vs. Exercise) or interaction (p \u3e 0.05). AUC for triglycerides (p = 0.057) and glucose (p = 0.243) were not significantly different between conditions. CONCLUSION: In the present analysis, exercise did not acutely affect cardiovascular or metabolic responses to a high-fat, high-sugar liquid meal. Larger sample sizes will facilitate better comparisons

Validity of a Novel Sensor for Noninvasive Measurement of Core Body Temperature in Humans during Exercise

The measurement of core body temperature during exercise can be useful for athletic performance and the prevention of heat-related illness. Non-invasive sensors have been developed for the measurement of core body temperature, but more data on their validity and reliability is needed before they can be recommended for widespread adoption. PURPOSE: The purpose of the present study was to evaluate a noninvasive core temperature sensor (TCore) during exercise compared to an ingestible thermistor (TPill). METHODS: Twenty men and women (25 ± 4 years) participated in this study. Participants completed 20 minutes of exercise at 60% age-predicted max heart rate, 20 minutes at 70%, and 20 minutes at 80% while wearing warm clothing. During exercise, heart rate, core temperature, RPE, and thermal comfort were collected every 5 minutes. Pre/post exercise changes in body mass and urine specific gravity were conducted to ensure stable fluid levels. Mean differences were compared via a paired t-test, core temperature during exercise using a time*device repeated measures ANOVA, and agreement assessed with Bland-Altman and correlation analysis. RESULTS: Participants lost -0.47 ± 0.42 % body mass during exercise. USG did not change in response to exercise (Pre: 1.009 ± 0.005 vs Post: 1.009 ± 0.006; p =0.93). Devices were well correlated (r = 0.90, 95% Confidence Interval: 0.74 – 0.97; p \u3c 0.0001). Mean core temperature during exercise was slightly but significantly lower as measured by the TCore compared to TPill (Mean difference = -0.3°C, 95% CI: -0.57 to -0.03; p = 0.028). Exercise created a main effect of time on core temperature (p \u3c 0.0001), with a significant interaction across time between devices (p \u3c 0.0001). Specifically, core temperature was lower for TCore from 15-55 minutes of exercise compared to TPill. Mean ± SD of bias was -0.3°C ± 0.16, with 95% limits of agreement of -0.61°C to 0.03°C. CONCLUSION: Results of the present investigation revealed that the CORE device tended to underestimate core body temperature during indoor exercise of increasing intensity. However, the margin of error was relatively small, and few participants exceeded 39°C. Future studies should conduct field validity tests of the CORE device and should also include measures of skin temperature to facilitate further comparisons

"Good" news from nowhere:imagining utopian sustainable accounting

Purpose The purpose of this paper is to attempt to provide a ray of hope, in the form of a Morris-style utopian dream of a sustainable world, as a basis for new forms of accounting and accountability in contemporary society. Design/methodology/approach The method is four-fold, weaving together an auto-ethnographic approach, a contextual dialogue between accounting academics and lobbyists, a Morris-inspired utopian metaphor and a stakeholder accountability event in the form of oral disclosures written as a song cycle. Findings Current efforts at integrated reporting are unlikely to change how large companies do business in order to address the risk of climate change in the short term. If the UN reports on climate change are correct, the authors need to take immediate action. The authors argue that, instead of waiting for climatic disaster to lead to a paradigm shift in corporate practice, “monetisation” of the costs of climate change is one way to encourage integrated thinking and sustainable business models. This relies on existing finance and accounting discourse to create a new “field of environmental visibility” which engenders environmental awareness on the part of the world’s companies and policy makers.Practical implications This utopian image may not appear a practicable, realistic solution to current problems but represents a starting point for optimism. It provides inspiration for policy makers to develop better forms of sustainability reporting, more suitable to the accelerating rates of climatic change. Originality/value To the authors’ knowledge this is the first attempt to develop Morris’s News From Nowhere as a basis for building new forms of accounting and accountability

Acute Effects of Different Inter-Repetition Rest Intervals During ‘Composite’ Training on Fast Stretch-Shortening Cycle and Neuromuscular Performance in Hurling Players: A Pilot Study

One study to date has compared inter-repetition rest intervals when employing ‘composite’ training. Thus, the purpose of this study was to compare the acute effects of 2-, 3- and 4-mins ‘composite’ training inter-repetition rest intervals on fast stretch shortening cycle (SSC) and neuromuscular performance. A randomized crossover research design was employed. Drop jump (DJ), 20m sprint (with 5 and 10m splits), countermovement jump (CMJ) and isometric mid-thigh pull (IMTP) tests were performed pre-session, post-session, and 7 days post-session to observe if supercompensation occurred. A 2-min rest interval showed enhancements in fast SSC DJ performance where supercompensation may have occurred in height, velocity, force and power (Cohen’s d = 0.22-0.55). A 3-minute rest interval elicited responses in 5 and 20m sprint performance (Cohen’s d = -0.29 to -0.30) and isometric RFD (Cohen’s d = 0.35-0.60) 7 days post-session. CMJ measures (Cohen’s d = 0.22-0.76) appeared to have experienced supercompensation when employing a 4-minute rest period. Significant (p < 0.05) decreases in performance pre- to post-session were found for certain sprint, CMJ and IMTP variables. The ‘composite’ training inter-repetition rest interval used, appears dependent on the primary goal of a training cycle. However, a 3-min rest interval may be used if there are multiple goals of a training cycle due to enhancements in sprint performance, isometric RFD and CMJ height. ‘Composite’ training is a time-efficient method of enhancing jump, sprint, and maximal strength, which is suitable for practitioners working in sports such as hurling where time is limited

Reactions to treatment debriefing among the participants of a placebo controlled trial

BACKGROUND: A significant proportion of trial participants respond to placebos for a variety of conditions. Despite the common conduct of these trials and the strong emphasis placed on informed consent, very little is known about informing participants about their individual treatment allocation at trial closure. This study aims to address this gap in the literature by exploring treatment beliefs and reactions to feedback about treatment allocation in the participants of a placebo-controlled randomized clinical trial (RCT). METHODS: Survey of trial participants using a semi-structured questionnaire including close and open-ended questions administered as telephone interviews and postal questionnaires. Trial participants were enrolled in a double-blind placebo-controlled RCT evaluating the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had closed and participants remained blind to treatment allocation. We assessed treatment expectations, the percentage of participants who wanted to be informed about their treatment allocation, their ability to guess and reactions to debriefing. RESULTS: Forty-six (73%) contactable participants responded to our survey. Forty-two were eligible (four participants with bilateral disease were excluded as they had received both treatments). Most (79%) participants did not have any expectations prior to receiving treatment, but many 'hoped' that something would help. Reasons for not having high expectations included the experimental nature of their care and possibility that they may get a placebo. Participants were hopeful because their pain was so severe and because they trusted the staff and services. Most (83%) wanted to be informed about their treatment allocation and study results. Over half (55%) said they could not guess which treatment they had been randomized to, and many of those who attempted a guess were incorrect. Reactions to treatment debriefing were generally positive, including in placebo responders. CONCLUSION: Our study suggests that most trial participants want to be informed about their treatment allocation and trial results. Further research is required to develop measure of hope and expectancy and to rigorously evaluate the effects of debriefing prospectively

The Atacama Cosmology Telescope: Cosmology from cross-correlations of unWISE galaxies and ACT DR6 CMB lensing

We present tomographic measurements of structure growth using cross-correlations of Atacama Cosmology Telescope (ACT) DR6 and Planck CMB lensing maps with the unWISE Blue and Green galaxy samples, which span the redshift ranges $0.2 \lesssim z \lesssim 1.1$ and $0.3 \lesssim z \lesssim 1.8$, respectively. We improve on prior unWISE cross-correlations not just by making use of the new, high-precision ACT DR6 lensing maps, but also by including additional spectroscopic data for redshift calibration and by analysing our measurements with a more flexible theoretical model. An extensive suite of systematic and null tests within a blind analysis framework ensures that our results are robust. We determine the amplitude of matter fluctuations at low redshifts ($z\simeq 0.2-1.6$), finding $S_8 \equiv \sigma_8 (\Omega_m / 0.3)^{0.5} = 0.813 \pm 0.021$ using the ACT cross-correlation alone and $S_8 = 0.810 \pm 0.015$ with a combination of Planck and ACT cross-correlations; these measurements are fully consistent with the predictions from primary CMB measurements assuming standard structure growth. The addition of Baryon Acoustic Oscillation data breaks the degeneracy between $\sigma_8$ and $\Omega_m$, allowing us to measure $\sigma_8 = 0.813 \pm 0.020$ from the cross-correlation of unWISE with ACT and $\sigma_8 = 0.813\pm 0.015$ from the combination of cross-correlations with ACT and Planck. These results also agree with the expectations from primary CMB extrapolations in $\Lambda$CDM cosmology; the consistency of $\sigma_8$ derived from our two redshift samples at $z \sim 0.6$ and $1.1$ provides a further check of our cosmological model. Our results suggest that structure formation on linear scales is well described by $\Lambda$CDM even down to low redshifts $z\lesssim 1$.Comment: 73 pages (incl. 30 pages of appendices), 50 figures, 16 tables, to be submitted to ApJ. Watch G. S. Farren and A. Krolewski discuss the analysis and results under https://cosmologytalks.com/2023/09/11/act-unwis

The Atacama Cosmology Telescope: Detection of Patchy Screening of the Cosmic Microwave Background

Spatial variations in the cosmic electron density after reionization generate cosmic microwave background anisotropies via Thomson scattering, a process known as the ``patchy screening" effect. In this paper, we propose a new estimator for the patchy screening effect that is designed to mitigate biases from the dominant foreground signals. We use it to measure the cross-correlation between \textit{unWISE} galaxies and patchy screening, the latter measured by the Atacama Cosmology Telescope and \textit{Planck} satellite. We report the first detection of the patchy screening effect, with the statistical significance of the cross-correlation exceeding $7\sigma$. This measurement directly probes the distribution of electrons around these galaxies and provides strong evidence that gas is more extended than the underlying dark matter. By comparing our measurements to electron profiles extracted from simulations, we demonstrate the power of these observations to constrain galaxy evolution models. Requiring only the 2D positions of objects and no individual redshifts or velocity estimates, this approach is complementary to existing gas probes, such as those based on the kinetic Sunyaev-Zeldovich effect.Comment: See Schutt et al for a detailed comparison of patchy screening estimators. 17 pages with 8 figure

Data Descriptor: Australia’s continental-scale acoustic tracking database and its automated quality control process

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the metadata files made available in this article.Our ability to predict species responses to environmental changes relies on accurate records of animal movement patterns. Continental-scale acoustic telemetry networks are increasingly being established worldwide, producing large volumes of information-rich geospatial data. During the last decade, the Integrated Marine Observing System’s Animal Tracking Facility (IMOS ATF) established a permanent array of acoustic receivers around Australia. Simultaneously, IMOS developed a centralised national database to foster collaborative research across the user community and quantify individual behaviour across a broad range of taxa. Here we present the database and quality control procedures developed to collate 49.6 million valid detections from 1891 receiving stations. This dataset consists of detections for 3,777 tags deployed on 117 marine species, with distances travelled ranging from a few to thousands of kilometres. Connectivity between regions was only made possible by the joint contribution of IMOS infrastructure and researcher-funded receivers. This dataset constitutes a valuable resource facilitating meta-analysis of animal movement, distributions, and habitat use, and is important for relating species distribution shifts with environmental covariates