Thermal evolution and resources of the Bowland Basin (NW England) from apatite fission-track analyses and multidimensional basin modelling

Once highlighted for having significant shale gas resource potential, the Bowland Basin has been at the centre of both scientific and political controversy over the last decade. Previous shale gas resource estimates range from 103 to 101 TCF. Repeated events of induced seismicity following hydraulic fracturing operations led to an indefinite government moratorium and abandonment of operations across the mainland UK. We use apatite fission-track analyses to investigate the magnitude and timing of post-Triassic uplift and exhumation. Results indicate that maximum palaeotemperatures of 90–100°C were reached in the stratigraphically younger Sherwood Sandstone. We combine palaeotemperature predictions to constrain palaeo heat flow and erosion in regional basin models for the first time. Our results indicate variable maximum Late Cretaceous palaeo heat flow values of 62.5–80 mW m−2 and the removal of 800–1500 m of post-Triassic strata at wells across the basin. Regional 2D basin modelling indicates a gas-in-place estimate of 131 ± 64 TCF for the Bowland Shale. This reduces to a resource potential of 13.1 ± 6.4 TCF, assuming a recovery factor of 10%. These values are significantly lower than previous resource estimates and reflect the highly complex nature of the Bowland Basin and relatively unknown history of post-Triassic uplift, exhumation and erosion

The Mechanisms Underlying the Beneficial Impact of Aerobic Training on Cancer-Related Fatigue: A Conceptual Review

Cancer-related fatigue (CRF) is a prevalent and persistent issue affecting cancer patients, with a broad impact on their quality of life even years after treatment completion. The precise mechanisms underlying CRF remain elusive, yet its multifaceted nature involves emotional, physical, and cognitive dimensions. The absence of effective medical treatments has prompted researchers to explore integrative models for potential insights. Notably, physical exercise emerges as a promising strategy for managing CRF and related symptoms, as studies showed a reduction in CRF ranging from 19% to 40%. Current recommendations highlight aerobic training at moderate intensity as beneficial, although questions about a dose–response relationship and the importance of exercise intensity persist. Despite the positive impact of exercise on CRF, the underlying mechanisms remain elusive. This review aims to provide a theoretical model explaining how aerobic exercise may alleviate CRF. Focusing on acute exercise effects, this review delves into the potential influence on peripheral and neural inflammation, immune function dysregulation, and neuroendocrine system disruptions. The objective is to enhance our understanding of the intricate relationship between exercise and CRF, ultimately paving the way for tailored interventions and potential pharmacological treatments for individuals unable to engage in physical exercise

7 avenue André Aune : Sénas, Bouches-du-Rhône (13), Provence-alpes-Côte d'Azur : rapport de diagnostic

Le diagnostic archéologique concerne le presbytère adossé à l’église St Amand, sa cour et une bande de terrain en retrait. Pour des raisons de sécurité, le bâtiment a été démoli peu avant l’opération et le diagnostic s’est donc concentré sur ses substructures. Une douzaine de tombes ont été détectées sous les derniers sols du presbytère, attestées par l’empreinte du creusement ou des dalles de couverture de pierre. Une seule a été fouillée, en coffre de pierre rudimentaire. Quelques tessons de céramique associés remontent au début du Moyen-âge (au plus tard XIIe siècle). Posé à même ce cimetière, certains murs recoupant des tombes, sur un terrain apparemment vierge de constructions, le presbytère, ne semble pas avoir été établi avant le XVIe siècle. Plusieurs états sont identifiables, les derniers sols conservés datent du XVIIIe siècle. Une élévation conservée sur un mur mitoyen présente un bel exemple d’utilisation du pisé, et ce sur une hauteur de 6,50 m. Enfin, un examen sommaire de l’élévation de l’église mise au jour par démolition du presbytère qui lui était adossé, révèle une multitude de phases constructives qui témoignent de l’histoire du bâtiment qu’il n’a pas été possible de documenter dans le cadre du diagnostic

7 avenue André Aune : Sénas, Bouches-du-Rhône (13), Provence-alpes-Côte d'Azur : rapport de diagnostic

Le diagnostic archéologique concerne le presbytère adossé à l’église St Amand, sa cour et une bande de terrain en retrait. Pour des raisons de sécurité, le bâtiment a été démoli peu avant l’opération et le diagnostic s’est donc concentré sur ses substructures. Une douzaine de tombes ont été détectées sous les derniers sols du presbytère, attestées par l’empreinte du creusement ou des dalles de couverture de pierre. Une seule a été fouillée, en coffre de pierre rudimentaire. Quelques tessons de céramique associés remontent au début du Moyen-âge (au plus tard XIIe siècle). Posé à même ce cimetière, certains murs recoupant des tombes, sur un terrain apparemment vierge de constructions, le presbytère, ne semble pas avoir été établi avant le XVIe siècle. Plusieurs états sont identifiables, les derniers sols conservés datent du XVIIIe siècle. Une élévation conservée sur un mur mitoyen présente un bel exemple d’utilisation du pisé, et ce sur une hauteur de 6,50 m. Enfin, un examen sommaire de l’élévation de l’église mise au jour par démolition du presbytère qui lui était adossé, révèle une multitude de phases constructives qui témoignent de l’histoire du bâtiment qu’il n’a pas été possible de documenter dans le cadre du diagnostic

Effects of combined exercise training on the inflammatory profile of older cancer patients treated with systemic therapy

Cancer-related fatigue (CRF) is a major issue in older cancer patients as it is associated with functional decline and a lower quality of life, and an increased inflammatory activity during cancer therapy is suspected to play a key role in CRF etiology. Combined aerobic and resistance exercise training is known to reduce CRF, and this could be mediated by a protective effect against this increased inflammatory activity. Hence, the main objective was to measure the effect of a 12-week combined exercise training on the inflammatory profile of older cancer patients undergoing systemic therapy. A secondary objective was to verify if there was an association between inflammatory profile and CRF. Methods: Twenty older non-metastatic cancer patients initiating chemotherapy and/or hormone therapy were randomly assigned to 12 weeks of supervised, combined exercise or a control group (static stretching). Primary outcomes were the inflammatory profile, Indoleamine 2,3-deoxygenase activity (KYN/TRP ratio), and CRF (FACIT-F questionnaire). Control outcomes were the fasting nutritional and hormonal blood profiles, body composition (iDXA), physical activity habits (PASE questionnaire), nutritional habits (3-day log), and treatment-related variables. Results: No worsening of the inflammatory profile was observed in both arms of the study after the intervention. No significant change in CRF was observed, although there was a trend for a reduction in the experimental group (p ​= ​0.10). Significant correlations were found at both timepoints between the KYN/TRP ratio and the delay with the previous treatment received (p ​≤ ​0.03). Conclusion: These results suggest that exercise might have elicited a positive effect on CRF, which was not mediated by the modulation of the pro-inflammatory cytokine profile. However, the decrease in IL-6/IL-10 ratio in the exercise group might reflect a possible anti-inflammatory effect of exercise. Moreover, exploratory analyses suggest that an acute effect of chemotherapy treatments influenced the inflammatory profile measurements, which could explain the absence of change in the fasting inflammatory profile

Characterization of the Cytotoxic T lymphocytes Acute Response Following Continuous Moderate Intensity and High Intensity Interval Exercise in Metastatic Cancer Patients Undergoing Chemotherapy

Background: Tumor-bearing animal studies have suggested that each aerobic exercise bout may acutely promote the infiltration of effector CD8+ cytotoxic T-cells (CTLs) in tumoral tissue and enhance the anti-tumor immune response. Exercise intensity being the main driver of this acute immune response, high-intensity interval exercise (HIIE) might be a promising strategy to stimulate anti-cancer immunity in cancer patients. Yet, so far, the acute effects of moderate continuous (MOD) and HIIE on circulating T-cells remain unknown in cancer patients receiving chemotherapy. Objective: To characterise the acute CTLs response following a MOD and a work matched HIIE trial in metastatic cancer patients undergoing chemotherapy. Methods: Eleven participants (45-65 years old) underwent a block-randomized crossover trial with a MOD and a duration and work-matched HIIE trial. Blood draws were performed before, after and 1h after each trial. Isolated peripheral blood mononuclear cells (PBMC) were stained to identify CTLs (CD3+CD8+), naive, central memory, effector memory (EM) and TEMRA (CCR7/CD45RA). EM and TEMRA were evaluated for their expression of CD28, PD-1, CD95, CXCR3 and CXCR4. Blood levels at each timepoint were computed using complete blood counts with leukocyte differentials. Results: Total, CD28-, CD95+ and CXCR3+ TEMRA CTLs blood levels increased immediately following both trials and decreased back to baseline levels 1h after exercise cessation (all p < 0.01). No statistically significant response to exercise was found in any of the EM subsets analyzed, although borderline significant post-exercise increases were found in PD-1+ EM cells (p = 0.052). Significant changes in the MFI values of these markers were found in both EM and TEMRA cells, suggesting that exercise may acutely modify the expression at the single cell level. Conclusion: In metastatic cancer patients, a MOD and a work-matched HIIE session both induced the preferential blood mobilization and egress of CXCR3+ TEMRA cells. This is consistent with the hypothesis that exercise might stimulate tumor infiltration by effector CTLs

Acute Natural Killer Cells Response to a Continuous Moderate Intensity and a Work-Matched High Intensity Interval Exercise Session in Metastatic Cancer Patients Treated With Chemotherapy

Background: It has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therapeutic approach in cancer patients. However, this immune response remains unstudied in cancer patients currently undergoing chemotherapy. Objective: To characterize the acute NK cell response following a moderate-intensity continuous aerobic exercise session (MOD), and a HIIE session in metastatic cancer patients treated with chemotherapy. Methods: Twelve cancer patients (45-65 years old) underwent a MOD and a duration and work-matched HIIE trial, in a block-randomized order. Peripheral blood mononuclear cells (PBMC) were isolated before, after and 1h after each trial. NK cell subsets were enumerated using flow cytometry and complete blood counts. The surface expression of the cytotoxic NK cell (cNK; CD56dimCD16+) subset was evaluated for its expression of the differentiation markers CD57 and CD158a, the activating receptor NKG2D, the immune checkpoints TIM-3 and PD-1, and the chemokine receptors CXCR3, CXCR4 and CCR2. Results: cNK cell blood counts increased immediately following MOD (p < 0.001) and decreased back to pre-exercise values one hour after exercise cessation (p < 0.001). The most responsive cNK cell subsets were expressing CD57, CD158a, NKG2D, TIM-3 and CXCR3. The HIIE trial elicited a similar biphasic response, without any difference between trials (all p ≥ 0.38). However, significant changes in the MFI values of CXCR4 and NKG2D were observed in the cNK cell subset following HIIE (all p ≤ 0.038), but not MOD. Conclusion: In metastatic cancer patients undergoing chemotherapy, both MOD and HIIE can elicit an acute mobilisation and egress of NK cells exhibiting phenotypic characteristics associated with high cytotoxicity and tumor homing. Future longitudinal trials are needed to determine if combining aerobic exercise training and chemotherapy will translate towards favorable immune and clinical outcomes