During our careers, we met Jean-François Muller essentially in the context of scientific meetings and PhD examination panels, in relation with the use of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. However, one of us (PCM) had also the opportunity to meet him in a less well-known aspect of his implication in societal activities related to the monitoring of air quality. In this recollection of Jean-François Muller, we would like to recall how his science has also served societal causes.

In this work, we study and solve the normalized Ricci flow equation for circle bundles over surfaces. Moreover, we study the asymptotic behavior of the solutions and their connections to some model geometries.

1. Tree growth–survival relationships link two demographic processes that dictate the com-position, structure and functioning of forest ecosystems. While these relationships have been shown to vary intra-specifically, it remains unclear how this reflects environmental variation and disturbance. We examined the influence of a 700-m elevation gradient and an Mw = 6.7 earthquake in 1994 on intra-specific variability in growth–survival relationships. We expected that survival models that incorporated recent growth would be better sup-ported than those using other factors known to influence tree survival. 2. We used a permanent plot network that representatively sampled a monodominant Nothofagus forest in New Zealand’s Southern Alps in 1974 and that was remeasured seven times through to 2009. The relationships were assessed using pre-earthquake growth and survival, pre-earthquake growth and post-earthquake survival (0–5 years post-earthquake), and post-earthquake growth and survival (5+ years post-earthquake). Sur-vival was related to growth of 4504 trees on 216 plots using Bayesian modelling. We hy-pothesised there would be a positive, logistic relationship between growth and survival. 3. Pre-earthquake, we found a positive, logarithmic growth–survival relationship at all eleva-tions. At higher elevations, trees grew more slowly but had higher survival, supporting our hypothesised demographic trade-off with elevation. As we expected, the earthquake al-tered the pre-earthquake growth–survival relationships and 0–5 years post-earthquake survival held little relationship with growth. Less expected was a strong, logarithmic growth–survival relationship that developed 5+ years post-earthquake because of en-hanced survival of fast-growing trees yet low survival of slow-growing trees. 4. Synthesis. Our findings demonstrate there can be trends in growth–survival relationships along an elevation gradient. If we assume a gradual climate warming is the equivalent of a forest stand shifting to a lower elevation, then data from our pre-earthquake period sug-gests that tree growth–survival relationships at any elevation could adjust to faster growth and lower survival. We also show how these novel growth–survival relationships could be altered by periodic disturbance.

The effects of climate change on coastal biodiversity are a major concern because altered community compositions may change associated rates of ecosystem functioning and services. While responses of single species or taxa have been studied extensively, it remains challenging to estimate responses to climate change across different levels of biological organisation. Studies that consider the effects of moderate realistic near-future levels of ocean warming and acidification are needed to identify scope for adaptation and evolution. Also, studies including different levels of biological complexity may reveal opportunities for amelioration or facilitation under changing environmental conditions. To test experimentally for independent and combined effects of predicted near-future warming and acidification on key benthic species, we manipulated three levels of temperature (ambient, +0.8 °C, +2 °C) and two levels of pCO2 (ambient at 450 ppm, elevated at 645 ppm) and quantified their effects on mussels and algae growing separately or together (to also test for inter-specific interactions). Warming increased mussel clearance and mortality rates simultaneously, which meant that total biomass peaked at + 0.8 °C. Surprisingly, however, no effects of elevated pCO2 were identified on mussels or algae. Moreover, when kept together, mussels and algae had mutually positive effects on each other’s performance (i.e. mussel survival and condition index, mussel and algal biomass, and proxies for algal productivity including relative maximum electron transport rate [rETRmax], saturating light intensity [Ik], and maximum quantum yield [Fv/Fm]), independent of warming and acidification. Our results show that even moderate warming affected the functioning of key benthic species, and we identified a level of resistance to predicted ocean acidification. Importantly, we show that the presence of a second functional group enhanced the functioning of both groups (mussels and algae), independent of changing environmental conditions, which highlights the ecological and potential economic benefits of conserving biodiversity in marine ecosystems.

Species-environment relationships have been extensively explored through species distribution models (SDM) and species abundance models (SAM), which have become key components to understand the spatial ecology and population dynamics directed at biodiversity conservation. Nonetheless, within the internal structure of species’ ranges, habitat suitability and species abundance do not always show similar patterns, and using information derived from either SDM or SAM could be incomplete and mislead conservation efforts. We gauged support for the abundance-suitability relationship and used the combined information to prioritize the conservation of South American dwarf caimans (Paleosuchus palpebrosus and P. trigonatus). We used 7 environmental predictor sets (surface water, human impact, topography, precipitation, temperature, dynamic habitat indices, soil temperature), 2 regressions methods (Generalized Linear Models - GLM, Generalized Additive Models - GAM), and 4 parametric distributions (Binomial, Poisson, Negative binomial, Gamma) to develop distribution and abundance models. We used the best predictive models to define 4 categories (low, medium, high, very high) to plan species conservation. The best distribution and abundance models for both Paleosuchus species included a combination of all predictor sets, except for the best abundance model for P. trigonatus which incorporated only temperature, precipitation, surface water, human impact, and topography. We found non-consistent and low explanatory power of environmental suitability to predict abundance which aligns with previous studies relating SDM-SAM. We extracted the most relevant information from each optimal SDM and SAM and created a consensus model (2,790,583 km2) that we categorized as low (39.6%), medium (42.7%), high (14.9%), and very high (2.8%) conservation priorities. We identified 279,338 km2 where conservation must be critically prioritized and only 29% of these areas are under protection. We concluded that optimal models from correlative methods can be used to provide a systematic prioritization scheme to promote conservation and as surrogates to generate insights for quantifying ecological patterns.

The spider genus Dysdera has undergone a remarkable diversification in the oceanic archipelago of the Canary Islands, ~60 endemic species originated during the 20 million years since the origin of the archipelago. This evolutionary radiation has been accompanied by substantial dietary shifts, often characterized by phenotypic modifications encompassing morphological, metabolic and behavioral changes. Hence, these endemic spiders represent an excellent model for understanding the evolutionary drivers and to pinpoint the genomic determinants underlying adaptive radiations. Recently, we achieved the first chromosome-level genome assembly of one of the endemic species, D. silvatica, providing a high-quality reference sequence for evolutionary genomics studies. Here, we conducted a low-coverage based resequencing study of a natural population of D. silvatica from La Gomera island. Taking advantage of the new high-quality genome, we characterized genome-wide levels of nucleotide polymorphism, divergence, and linkage disequilibrium, and inferred the demographic history of this population. We also performed comprehensive genome-wide scans for recent positive selection. Our findings uncovered exceptionally high levels of nucleotide diversity and recombination in this geographically restricted endemic species, indicative of large historical effective population sizes. Furthermore, we identified genomic regions potentially under positive selection, shedding light on relevant biological processes, such as vision and nitrogen extraction as possible targets of adaptation and eventually, as drivers of the species diversification. This pioneering study in spiders endemic of an oceanic archipelago lays the groundwork for broader population genomics investigations aimed at understanding the genetic mechanisms driven adaptive radiations in island ecosystems.

Title PageManuscript type Case Report

Aim: Currently, therapeutic drug monitoring for astronauts faces limitations in conventional blood sampling and sample management onboard the international space station. Here, we explore the feasibility of dried blood spot (DBS) collection method during parabolic flights (PF) to overcome these constraints. Methods: We assessed the feasibility of blood deposition on blotting paper for preanalytical aspects in a PF using synthetic blood. Subsequently, DBS sampling validation was carried out in another PF campaign. Twenty volunteers participated in a pharmacokinetic study on caffeine and its metabolite, paraxanthine (as proof of concept), conducted during parabolic flights. After >18h caffeine washout, coffee (115 mg) or tea (30 mg), or 3 dark chocolate squares (11 mg) were administered. DBS samples were collected at baseline, during weightlessness, and post-flight. Caffeine and paraxanthine were analyzed using liquid chromatography-tandem mass spectrometry. Genotyping for Cytochrome P450-1A2 (CYP1A2) was performed and a metabolic ratio by areas under the curves for caffeine and paraxanthine (AUCPAX/AUCCAF) for CYP1A2 was determined. User experience survey was also conducted. Results: Full in-flight pharmacokinetic was feasible in 17 volunteers with 3 failures due to motion-sickness. We observed expected differences in kinetic profiles, consistent with consumption habits, the ingested dose and the genotypic/phenotypic information. The metabolic ratio did not significantly differ between parabolic flights conditions and ground conditions. Overall participants were satisfied with the usability of the method. Conclusion: DBS collection was safe, stable, feasible and well accepted in weightlessness. This method would offer valuable insights into human metabolism adaptation during long-term spaceflight, addressing space pharmacology challenges.

Medication errors cause preventable patient harm with annual costs of USD$42 billion globally. In England, 237 million errors occur annually, accounting for 1700 deaths, with trainee doctors being responsible for the highest proportion of errors. The UK introduced the national Prescribing Safety Assessment (PSA) in 2013 to ensure prescribing competency. Imperial College School of Medicine (ICSM) sought to increase learning opportunities and reduce errors through a monthly Prescribing Practice Questions (PPQs) programme. PSA scores from 2020 (prior to PPQ introduction) to 2024 (first cohort to receive entire PPQ programme), the prescription writing skills (PWS) subsection and applied knowledge test (AKT) scores in 2020 and 2024 were analysed. 1505 students sat the PSA between 2020 and 2024. PSA fails significantly reduced from 2.51% in 2020 to 0% in 2024 (p=0.0054). Median PSA scores significantly improved from 78.5% in 2020 to 84.0% in 2024 (p<0.0001). Median AKT scores decreased between 2020 and 2024 (78.0% vs 74.5%, p<0.0001). Absolute increase in PSA scores from lowest to highest quintiles was 10 percentage points (pp), 7pp, 5pp, 4pp and 1pp, respectively, between 2020 and 2024. Median PWS scores significantly improved from 76.3 % (61/80) in 2020 to 87.5% (70/80) in 2024 (p<0.0001). Since introducing PPQs, PSA and PWS scores have statistically significantly improved, with progressively greater impact on students at the bottom of the performance distribution. Early, targeted and repeated opportunities for authentic prescribing activities, such as the PPQs, in undergraduate training may lead to significant improvement in prescribing competency as determined by the PSA.

Regulating lithium (Li) plating/stripping behavior in three-dimensional (3D) conductive scaffolds is critical to stabilize Li metal batteries (LMBs). Surface protrusions and roughness in these scaffolds can induce uneven distributions of the electric fields and ionic concentrations, forming ’hot spots’. Hot spots may cause uncontrollable Li dendrites growth, presenting significant challenges to the cycle stability and safety of LMBs. To address these issues, we construct a Li ionic conductive-dielectric gradient bifunctional interlayer (ICDL) onto 3D Li-injected graphene/carbon nanotube scaffold (LGCF) via in situ reaction of exfoliated hexagonal boron nitride (fhBN) and molten Li. Microscopic and spectroscopic analyses reveal that ICDL consists of fhBN-rich outer layer and inner layer enriched with Li3N and Li-boron composites (Li-B). The outer layer utilizes dielectric properties to effectively homogenize the electric field, while the inner layer ensures high Li ion conductivity. Moreover, DFT calculations indicate that ICDL can effectively adsorb Li and decrease the Li diffusion barrier, promoting enhanced Li ion transport. The modulation of Li kinetics by ICDL increases the critical length of the Li nucleus, enabling suppression of Li dendrite growth. Attributing to these advantages, the ICDL coated LGCF (ICDL@LGCF) demonstrates impressive long term cycle performances in both symmetric cells and full cells.

Optimizing charging protocols is critical for reducing battery charging time and decelerating battery degradation in applications such as electric vehicles. Recently, reinforcement learning (RL) methods have been adopted for such purposes. However, RL-based methods may not ensure system (safety) constraints, which can cause irreversible damages to batteries and reduce their lifetime. To this end, this work proposes an adaptive and safe RL framework to optimize fast charging strategies while respecting safety constraints with a high probability. In our method, any unsafe action that the RL agent decides will be projected into a safety region by solving a constrained optimization problem. The safety region is constructed using adaptive Gaussian process (GP) models, consisting of static and dynamic GPs, that learn from online experience to adaptively account for any changes in battery dynamics. Simulation results show that our method can charge the batteries rapidly with constraint satisfaction under varying operating conditions.

Key points: 1. Tonsillectomy is associated with risks, including primary and secondary haemorrhage, frequently requiring readmissions and methods that minimise these risks should be advocated. 2. The current analysis includes a data set of 953 children who underwent tonsillectomy using cold-steel dissection technique   3.  Nine patients (1%) were readmitted, one for infection and 8 (0.8%) for haemorrhage. One (0.1%) patient suffered primary haemorrhage and required conservative management only. 4. The commonest indication for surgery was recurrent acute tonsillitis and all the patients with post tonsillectomy haemorrhage were from this group. Obesity and obstructive sleep apnoea did not adversely affect outcome. 5. None of the patients in this study population needed reoperation to control bleeding. Cold steel dissection tonsillectomy, combined with a strict protocol produced very few complications in these series.

Salvage En Bloc Resection for Refractory Recurrent Pure Testicular Seminoma: A Case Report

Title:

The suprachiasmatic nucleus (SCN) is the master clock that orchestrates circadian clocks across the body to synchronize with and anticipate the earth’s light/dark cycles. Although post-transcriptional regulators called microRNAs have been implicated in physiological SCN function, how the absence of the entire mature miRNome impacts SCN output has not yet been explored. Here, we have generated an SCN-specific Dicer knockout mouse model by crossing Syt10Cre mice with Dicerflox mice to study behavioral consequences of miRNA depletion in the SCN. We show that loss of all mature miRNAs in the SCN shortens the circadian period length by ~40 minutes at the tissue level, and by ~50 minutes at the locomotor activity level. Knockout animals also showed arrythmicity or ultradian locomotor activities with no light masking under constant light, a condition which usually caused lengthening of the circadian period length and reduced activities, i.e. light masking, in nocturnal animals. Moreover, induction of Dicer knockout by Cre injection into the SCN of adult Dicerflox mice eventually resulted in loss of behavioral rhythms. Finally, we show suggestive evidence that SCN desynchronization might be one mechanism underlying the behavioral phenotypes of SCN-specific Dicer knockout animals.

A document by Bibek Shrestha. Click on the document to view its contents.

Incorporating Innovative B-Cell Targeting Therapeutics into a Combined-Modality Bridging Approach Followed by Timely Consolidative Haploidentical Transplantation to Salvage a Pediatric Patient with Relapsed/Refractory Diffuse Large B-Cell LymphomaYu-Ju Chao1, Pei-Ing Lee2, Tzu-Hsien Yang3, Li-Hua Fang4, Yu-Chun Tsai5, Ming-Yuan Lee6, Yun-Hsin Wang7, Liuh-Yow Chen3, and Rong-Long Chen1*1Department of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan2Department of Nuclear Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan3 Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan4Department of Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan5Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan6Department of Pathology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan7Department of Molecular Medicine, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan*Corresponding author: RL ChenName : Rong-Long Chen, M.D.Tel. no. : 886-2-2897-0011; Fax no. : 886-2-2896-2591E-mail : [email protected] : No. 125, Lih-Der Road, Pei-Tou District, Taipei, Taiwan, 11259Word count : Main text (excludes Title page, Abstract, Conflicts of Interest Statement, Acknowledgments, References, Tables, Figures, and Legends) 850.Number of Tables, Figures, and Supporting Information files: 2Running title : Novel Salvage of Resistant Large Cell lymphomaKeywords : Antibody-drug conjugates; chimeric antigen receptor T-cells; diffuse large B-cell lymphoma; HLA haplo-identical transplantation; childhood; peripheral blood stem cell transplantation.

Additive Manufacturing(AM) has revolutionized the production industry by offering design freedom with shorter lead times and reduced material wastage. However, the damage tolerance of AM parts is a significant concern due to their microstructural and geometric complexities, which affect their mechanical performance. This article aims to provide a comprehensive overview of the manufacturing parameters affecting the damage tolerance of components produced by AM specifically selective laser melting(SLM). Detailed discussions are presented on the effects of manufacturing attributes on the microstructure, defects, and mechanical characteristics of AM parts. Depending on these aspects, basic concepts are studied and critically explained specifically for AM materials. The basic criterion for damage-tolerant component design, the criterion for fatigue and fracture properties, and the effect of the defects on fatigue life are critically presented. In addition, the effect of different types of gradation on the crack growth behavior of AM samples processed by SLM is also investigated in depth. There is currently a lack of a specific review study in the literature that establishes a connection between process attributes and metallographic properties, and their impact on the damage behavior of additively manufactured parts. This gap in research highlights the need for a comprehensive review to bridge this knowledge deficit and provide valuable insights for understanding the relationships between manufacturing processes, material characteristics, and the structural integrity of additively manufactured components. This review concludes by addressing the challenges and opportunities in designing and qualifying AM parts for damage tolerance.