Global decarbonization potential of CO2 mineralization in concrete materials.

CO2 mineralization products are often heralded as having outstanding potentials to reduce CO2-eq. emissions. However, these claims are generally undermined by incomplete consideration of the life cycle climate change impacts, material properties, supply and demand constraints, and economic viability of CO2 mineralization products. We investigate these factors in detail for ten concrete-related CO2 mineralization products to quantify their individual and global CO2-eq. emissions reduction potentials. Our results show that in 2020, 3.9 Gt of carbonatable solid materials were generated globally, with the dominant material being end-of-life cement paste in concrete and mortar (1.4 Gt y-1). All ten of the CO2 mineralization technologies investigated here reduce life cycle CO2-eq. emissions when used to substitute comparable conventional products. In 2020, the global CO2-eq. emissions reduction potential of economically competitive CO2 mineralization technologies was 0.39 Gt CO2-eq., i.e., 15% of that from cement production. This level of CO2-eq. emissions reduction is limited by the supply of end-of-life cement paste. The results also show that it is 2 to 5 times cheaper to reduce CO2-eq. emissions by producing cement from carbonated end-of-life cement paste than carbon capture and storage (CCS), demonstrating its superior decarbonization potential. On the other hand, it is currently much more expensive to reduce CO2-eq. emissions using some CO2 mineralization technologies, like carbonated normal weight aggregate production, than CCS. Technologies and policies that increase recovery of end-of-life cement paste from aged infrastructure are key to unlocking the potential of CO2 mineralization in reducing the CO2-eq. footprint of concrete materials.

To burn or not to burn: similar effects of different types of prenatal tobacco exposure on infant lung function.

The first study to describe the harmful effects of snus on the unborn infant provides evidence to help clinicians and mothers collectively to make an informed choice about quitting the use of snus before planning pregnancies https://bit.ly/3vJnBxW.

Changes in Rates of Suicide by Mass Shooters, 1980-2019.

OBJECTIVE: The rate of worldwide mass shootings increased almost 400% over the last 40 years. About 30% are followed by the perpetrator's fatal or nonfatal suicide attempt. METHOD: We examined the rate of fatal and nonfatal attempts among 528 mass shooters over the last 40 years and their relationship to detected mental illness to better understand this specific context of suicide. We collected information on U.S.-based, personal-cause mass murders that involved one or more firearms, from online sources. RESULTS: A greater proportion of mass shooters from 2000 to 2019 took or attempted to take their own lives (40.5%) compared with those from 1980 to 1999 (23.2%, p < 0.001). More than double the proportion of perpetrators who made a fatal or nonfatal suicide attempt had a history of non-psychotic psychiatric/neurologic symptoms (38.9%), compared with perpetrators who did not make a fatal or nonfatal suicide attempt (18.1%; p < 0.001). Among mass shooters who made fatal or nonfatal suicide attempts, 77 of 175 (44%) did not have any recorded psychiatric, neurologic, or substance use condition. Of the 98 mass shooters who made fatal or non-fatal suicide attempts and had a psychiatric, substance use, or neurologic condition, 41 had depressive disorders. CONCLUSION: It is possible that a lack of information about the perpetrators' mental health or suicidal ideation led to an underestimation of their prevalence. These data suggest that suicide associated with mass shootings may represent a specific context for suicide, and approaches such as psychological autopsy can help to ascertain when psychiatric illness mediates the relationship between mass shootings and suicide.

We examined 528 mass shootings.A greater proportion of mass shooters from 2000-2019 made a fatal or nonfatal suicide attempt (123/304, 40.5%) compared with mass shooters from 1980-1999 (52/224, 23.2%), χ2 = 17.3, p<.001.More than double the proportion of perpetrators who made a fatal or nonfatal suicide attempt had a history of non-psychotic psychiatric/neurologic symptoms (38.9%), compared with those who did not (18.1%; p < 0.001).Among mass shooters who made a fatal or nonfatal suicide attempt, 77 of 175 (44%) did not have any recorded psychiatric, neurologic, or substance use condition. However, it is possible that a lack of information about the perpetrators' mental health or suicidal ideation led to an underestimation of their prevalence.These results suggest that perpetrators may have considered suicide a potential outcome of such an event, and/or that the perpetrators' high levels of aggression and anger, accompanied by an impaired capacity for restraint, resulted in homicide followed by suicidal behavior.Psychological autopsies can clarify the role of psychiatric illness and more extreme aggressive traits in homicide-suicide instances of mass shootings.

Clinician Perspectives on Suicide Safety Planning and Its Implementation.

OBJECTIVE: The safety planning intervention is an evidence-based practice shown to reduce suicide risk, but implementation of high-quality safety planning has proven challenging. We aimed to understand clinician perspectives on the safety planning intervention to inform future implementation efforts. METHOD: This cross-sectional survey of clinicians who care for patients at risk of suicide in an academic medical center asked about comfort levels and fidelity to components of the safety planning intervention and assessed implementation barriers and facilitators. We used exploratory data analysis and regression analysis to explore clinician perspectives and assess the relationship between formal training and implementation. RESULTS: Ninety-two clinicians responded to the survey. Two-thirds of participants (64.9%) endorsed using all six core elements of the safety planning intervention. Participants who reported receiving formal training in safety planning were significantly more likely to report being comfortable completing a safety plan (p < .001); those with higher levels of comfort were significantly more likely to endorse using all of the core elements of the safety planning intervention (p < .001). CONCLUSIONS: Training in the evidence-based safety planning intervention is associated with clinician comfort and awareness of the core elements of the intervention. Our results suggest that there are gaps in clinician training and that formal safety planning intervention training could have a positive effect on clinician comfort and treatment fidelity.

Good Psychiatric Management of Borderline Personality Disorder: Foundations and Future Challenges.

Borderline personality disorder is a common condition characterized by numerous comorbid conditions, frequent use of clinical services, and an elevated lifetime risk for suicide. Good psychiatric management (GPM) was developed for patients with borderline personality disorder with the purpose of supporting wider community adoption and dissemination compared with existing therapies. The authors aimed to review the foundations and development of GPM, in particular the initial Canadian study assessing the therapy. They then reviewed the progress in research arising from the initial study and explored the research and educational opportunities needed to further the development of GPM for patients with borderline personality disorder. Research has indicated that patients with borderline personality disorder with complex comorbid conditions and impulsivity may benefit from GPM. Future research needs include noninferiority and equivalence studies comparing GPM with another evidence-based treatment; studies demonstrating that evidence-based therapies for borderline personality disorder improve functioning; and research on more accessible therapies, mechanisms of action for evidence-based therapies, extending therapies to patients with borderline personality disorder and significant comorbid conditions, and modifying therapies for men with borderline personality disorder. Attention should be directed toward testing stepped care models and integrating therapies such as GPM into psychiatric training programs. GPM is in development but shows promise as a therapy that is effective and accessible and that can be widely disseminated.

Examining the feasibility and utility of heart rate variability on intervention outcomes targeting emotion regulation in autism: a brief report.

Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body's primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8-17 years who participated in the pilot study of Regulating Together, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test-retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.

Actinyl Electronic Structure Probed by XAS: The Role of Many-Body Effects.

A detailed analysis of the wave functions for the M5 to 5f excitations in the linear actinyls, UO22+, NpO22+, and PuO22+, and the theoretical X-ray absorption spectra obtained with these wave functions in comparison with experimental M5-edge high-resolution X-ray absorption near-edge structure (HR-XANES) spectra is presented. The wave functions include full treatment of scalar and spin-orbit relativistic effects through the use of a Dirac-Coulomb Hamiltonian; many-body effects are included in determining the wave functions. The character of the excited states and of the active spaces to describe the wave functions for these states are investigated and analyzed. It is shown that the excited states cannot, in general, be described with a single configuration but have an essential multiconfiguration character. The characterization of the properties of the excited states and the X-ray absorption spectra was achieved through the use of novel methods.

CoRAL accurately resolves extrachromosomal DNA genome structures with long-read sequencing.

Extrachromosomal DNA (ecDNA) is a central mechanism for focal oncogene amplification in cancer, occurring in approximately 15% of early-stage cancers and 30% of late-stage cancers. EcDNAs drive tumor formation, evolution, and drug resistance by dynamically modulating oncogene copy-number and rewiring gene-regulatory networks. Elucidating the genomic architecture of ecDNA amplifications is critical for understanding tumor pathology and developing more effective therapies. Paired-end short-read (Illumina) sequencing and mapping have been utilized to represent ecDNA amplifications using a breakpoint graph, where the inferred architecture of ecDNA is encoded as a cycle in the graph. Traversals of breakpoint graph have been used to successfully predict ecDNA presence in cancer samples. However, short-read technologies are intrinsically limited in the identification of breakpoints, phasing together of complex rearrangements and internal duplications, and deconvolution of cell-to-cell heterogeneity of ecDNA structures. Long-read technologies, such as from Oxford Nanopore Technologies, have the potential to improve inference as the longer reads are better at mapping structural variants and are more likely to span rearranged or duplicated regions. Here, we propose CoRAL (Complete Reconstruction of Amplifications with Long reads), for reconstructing ecDNA architectures using long-read data. CoRAL reconstructs likely cyclic architectures using quadratic programming that simultaneously optimizes parsimony of reconstruction, explained copy number, and consistency of long-read mapping. CoRAL substantially improves reconstructions in extensive simulations and 10 datasets from previously-characterized cell lines as compared to previous short and long-read based tools. As long-read usage becomes wide-spread, we anticipate that CoRAL will be a valuable tool for profiling the landscape and evolution of focal amplifications in tumors.

100-kHz carbon monoxide TP-PLIF imaging using ultra-narrow-linewidth burst-mode OPO.

A 100-kHz rate two-photon planar laser-induced fluorescence (TP-PLIF) imaging of carbon monoxide (CO) is successfully demonstrated utilizing a narrow-linewidth optical parametric oscillator (OPO) generating light at ∼230.1 nm. A specially designed injection-seeded burst-mode OPO was constructed and characterized for this purpose. This OPO efficiently converts the 355-nm output of a high-energy nanosecond burst-mode laser to ∼230.1 nm following parametric splitting and mixing processes. Generation of an ultra-narrow-linewidth 230.1 nm laser pulse is crucial for effectively exciting CO via a two-photon process from the ground X1Σ+ to the B1Σ+ electronic state-enabling PLIF imaging over a large area. The experimental setup is capable of tracking high-speed flow structures of a CO/N2 mixture, showcasing detection speeds 100 times greater than those achieved with previous femtosecond laser sources. This substantial increase in repetition rate will allow time-resolved CO-TP-PLIF measurements in highly dynamic hypersonic boundary layers and detonation-driven combustion processes for revealing chemical kinetics and turbulent aerodynamics.

Microbiome Dynamics and Functional Composition in Coelopa frigida (Diptera, Coelopidae): Insights into Trophic Specialization of Kelp Flies.

Coelopidae (Diptera), known as kelp flies, exhibit an ecological association with beached kelp and other rotting seaweeds. This unique trophic specialization necessitates significant adaptations to overcome the limitations of an algal diet. We aimed to investigate whether the flies' microbiome could be one of these adaptive mechanisms. Our analysis focused on assessing composition and diversity of adult and larval microbiota of the kelp fly Coelopa frigida. Feeding habits of the larvae of this species have been subject of numerous studies, with debates whether they directly consume kelp or primarily feed on associated bacteria. By using a 16S rRNA metabarcoding approach, we found that the larval microbiota displayed considerably less diversity than adults, heavily dominated by only four operational taxonomic units (OTUs). Phylogenetic placement recovered the most dominant OTU of the larval microbiome, which is the source of more than half of all metabarcoding sequence reads, as an undescribed genus of Orbaceae (Gammaproteobacteria). Interestingly, this OTU is barely found among the 15 most abundant taxa of the adult microbiome, where it is responsible for less than 2% of the metabarcoding sequence reads. The other three OTUs dominating the larval microbiome have been assigned as Psychrobacter (Gammaproteobacteria), Wohlfahrtiimonas (Gammaproteobacteria), and Cetobacterium (Fusobacteriota). Moreover, we also uncovered a distinct shift in the functional composition between the larval and adult stages, where our taxonomic profiling suggests a significant decrease in functional diversity in larval samples. Our study offers insights into the microbiome dynamics and functional composition of Coelopa frigida.

Sarcoma_CellminerCDB: A tool to interrogate the genomic and functional characteristics of a comprehensive collection of sarcoma cell lines.

Sarcomas are a diverse group of rare malignancies composed of multiple different clinical and molecular subtypes. Due to their rarity and heterogeneity, basic, translational, and clinical research in sarcoma has trailed behind that of other cancers. Outcomes for patients remain generally poor due to an incomplete understanding of disease biology and a lack of novel therapies. To address some of the limitations impeding preclinical sarcoma research, we have developed Sarcoma_CellMinerCDB, a publicly available interactive tool that merges publicly available sarcoma cell line data and newly generated omics data to create a comprehensive database of genomic, transcriptomic, methylomic, proteomic, metabolic, and pharmacologic data on 133 annotated sarcoma cell lines. The reproducibility, functionality, biological relevance, and therapeutic applications of Sarcoma_CellMinerCDB described herein are powerful tools to address and generate biological questions and test hypotheses for translational research. Sarcoma_CellMinerCDB (https://discover.nci.nih.gov/SarcomaCellMinerCDB) aims to contribute to advancing the preclinical study of sarcoma.

Dysfunction of infiltrating cytotoxic CD8+ T cells within the graft promotes murine kidney allotransplant tolerance.

Tolerance of mouse kidney allografts arises in grafts that develop regulatory Tertiary Lymphoid Organs (rTLOs). scRNAseq data and adoptive transfer of alloreactive T cells post-transplant showed that cytotoxic CD8+ T cells are reprogrammed within the accepted graft to an exhausted/regulatory-like phenotype mediated by IFN-γ. Establishment of rTLOs was required since adoptive transfer of alloreactive T cells prior to transplantation results in kidney allograft rejection. Despite intragraft CD8+ cells with a regulatory phenotype, they were not essential for the induction and maintenance of kidney allograft tolerance since renal allotransplantation into CD8 KO recipients resulted in acceptance and not rejection. Analysis of scRNAseq data from allograft kidneys and malignant tumors identified similar regulatory-like cell types within the T cell clusters and trajectory analysis showed that cytotoxic CD8+ T cells are reprogrammed into an exhausted/regulatory-like phenotype intratumorally. Induction of cytotoxic CD8+ T cell dysfunction of infiltrating cells appears to be a beneficial mechanistic pathway that protects the kidney allotransplant from rejection through a process we call "defensive tolerance." This pathway has implications for our understanding of allotransplant tolerance and tumor resistance to host immunity.

The birth prevalence of congenital hyperinsulinism: a narrative review of the epidemiology of a rare disease.

Background Congenital hyperinsulinism (HI) is a rare pediatric disease and the most common cause of severe, persistent hypoglycemia in childhood. It is characterized by the dysregulation of insulin secretion from the pancreas and can lead to irreversible brain damage with lifelong neurodisability. Summary The global birth prevalence of HI is currently unknown. An evidence-based estimate of HI birth prevalence is essential to improve diagnosis and patient management, to drive clinical research and the development of new treatments, and to inform public policy. In order to estimate the birth prevalence of persistent HI, a targeted literature review of studies that report HI epidemiological data was undertaken, and the strengths and limitations of each study were analyzed. Overall, eight global studies were identified that reported independently determined HI epidemiological data. Key messages The best estimate for the birth prevalence of persistent HI in European-ancestry populations is 3.5 per 100,000 births. Local consanguinity patterns appear to have a considerable impact on the birth prevalence of persistent HI in each country, precluding the application of this figure to all global populations. More epidemiological studies with robust methodology are needed to enable a reliable approximation of the incidence and prevalence of HI in global populations.

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity.

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation. Studying the neural mechanisms underlying sound sensitivity in FXS using scalp electroencephalography (EEG) is challenging because the temporal and frontal regions have overlapping neural projections that are difficult to differentiate. To overcome this challenge, we conducted EEG source analysis on a group of 36 individuals with FXS and 39 matched healthy controls. Our goal was to characterize the spatial and temporal properties of the response to an auditory chirp stimulus. Our results showed that males with FXS exhibit excessive activation in the frontal cortex in response to the stimulus onset, which may reflect changes in top-down modulation of auditory processing. Additionally, during the chirp stimulus, individuals with FXS demonstrated a reduction in typical gamma phase synchrony, along with an increase in asynchronous gamma power, across multiple regions, most strongly in temporal cortex. Consistent with these findings, we observed a decrease in the signal-to-noise ratio, estimated by the ratio of synchronous to asynchronous gamma activity, in individuals with FXS. Furthermore, this ratio was highly correlated with performance in an auditory attention task. Compared to controls, males with FXS demonstrated elevated bidirectional frontotemporal information flow at chirp onset. The evidence indicates that both temporal lobe hyperexcitability and disruptions in top-down regulation play a role in auditory sensitivity disturbances in FXS. These findings have the potential to guide the development of therapeutic targets and back-translation strategies.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy.

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking. Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy. Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months. Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection. Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively. Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89). Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Manipulating mitochondrial pyruvate carrier function causes metabolic remodeling in corneal myofibroblasts that ameliorates fibrosis.

Myofibroblasts are key cellular effectors of corneal wound healing from trauma, surgery, or infection. However, their persistent deposition of disorganized extracellular matrix can also cause corneal fibrosis and visual impairment. Recent work showed that the PPARγ agonist Troglitazone can mitigate established corneal fibrosis, and parallel in vitro data suggested this occurred through inhibition of the mitochondrial pyruvate carrier (MPC) rather than PPARγ. In addition to oxidative phosphorylation (Ox-Phos), pyruvate and other mitochondrial metabolites provide carbon for the synthesis of biological macromolecules. However, it is currently unclear how these roles selectively impact fibrosis. Here, we performed bioenergetic, metabolomic, and epigenetic analyses of corneal fibroblasts treated with TGF-ß1 to stimulate myofibroblast trans-differentiation, with further addition of Troglitazone or the MPC inhibitor UK5099, to identify MPC-dependencies that may facilitate remodeling and loss of the myofibroblast phenotype. Our results show that a shift in energy metabolism is associated with, but not sufficient to drive cellular remodeling. Metabolites whose abundances were sensitive to MPC inhibition suggest that sustained carbon influx into the Krebs' cycle is prioritized over proline synthesis to fuel collagen deposition. Furthermore, increased abundance of acetyl-CoA and increased histone H3 acetylation suggest that epigenetic mechanisms downstream of metabolic remodeling may reinforce cellular phenotypes. Overall, our results highlight a novel molecular target and metabolic vulnerability that affects myofibroblast persistence in the context of corneal wounding.