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The application of carbonate clumped isotope (Δ47) thermometry in deep-time is often limited by modification of the original temperature signal by thermal resetting. New modeling approaches to estimate the initial isotopic composition of partially reset calcites and maximal burial temperatures, however, open promising avenues in temperature reconstruction. Such approaches strongly depend on laboratory-derived kinetic parameters of calcite materials, which may differ in their microstructure, water content and distribution, and minor and trace element composition, and thus may have different resetting kinetics. The rostra of belemnites, an extinct group of mollusks with a wide temporal and spatial occurrence in the Mesozoic, have been extensively used for deep-time paleoclimate reconstructions using oxygen isotope geochemistry. Belemnites are also important targets for clumped isotope-based temperature reconstructions, but often are found to have reset Δ47 compositions. Here, we present results from heating experiments on belemnite rostral calcite and optical calcite and provide belemnite-specific kinetic parameters for clumped isotope resetting. We show that belemnite calcite is altered faster and at lower temperatures than optical calcite and all other calcites reported in previous studies. We suggest that fast initial resetting results from oxygen isotope exchange of belemnite calcite with internal skeletal water present as fluid inclusions or organic-derived water, a process completed within 2–4 min at the experimental temperatures used here. Extrapolation to geological timescales using different solid-state bond reordering models shows that belemnite calcite resetting starts at lower burial temperatures than brachiopod, spar, and optical calcites. This susceptibility to thermal resetting results in a measurable (+3 ◦C) increase of the apparent Δ47 temperature even under shallow to moderate burial conditions (i.e., 40–50 ◦C for 106–107 years timescales). Following the overprint to higher apparent Δ47 temperatures during burial, the belemnite Δ47 may further reequilibrate during exhumation resulting in a decrease of apparent Δ47 temperatures. Such “retrograde resetting” is similar to what is observed for carbonatites and marbles during cooling, and may cause underestimation of the thermal resetting a sample experienced during its geological history. Overall, our results demonstrate the importance of material-specific kinetic parameters and we urge caution when interpreting Δ47-derived temperatures of biogenic carbonates from deep-time archives., Swiss National Science Foundation project number 200021_169849, AF from Juan de la Cierva Fellowship (IJC2019040065-I), Spanish Ministry of Science and Innovation, European Development Fund and the European Social Fund, The European Commission, Horizon 2020 (ICECAP; grant no. 101024218), The Research Council of Norway Centre of Excellence funding scheme, Project number 223272. EBSD data for the WA-CB-11 brachiopod provided by the authors of Henkes et al. (2014), US National Science Foundation (EAR-1226832)

Elementary events that determine photochemical outcomes and molecular functionalities happen on the femtosecond and subfemtosecond timescales. Among the most ubiquitous events are the nonadiabatic dynamics taking place at conical intersections. These facilitate ultrafast, nonradiative transitions between electronic states in molecules that can outcompete slower relaxation mechanisms such as fluorescence. The rise of ultrafast X-ray sources, which provide intense light pulses with ever-shorter durations and larger observation bandwidths, has fundamentally revolutionized our spectroscopic capabilities to detect conical intersections. Recent theoretical studies have demonstrated an entirely new signature emerging once a molecule traverses a conical intersection, giving detailed insights into the coupled nuclear and electronic motions that underlie, facilitate, and ultimately determine the ultrafast molecular dynamics. Following a summary of current sources and experiments, we survey these techniques and provide a unified overview of their capabilities. We discuss their potential to dramatically increase our understanding of ultrafast photochemistry.

The tumor microenvironment is necessary for recapitulating the intratumoral heterogeneity and cell state plasticity found in human primary glioblastoma (GBM). Conventional models do not accurately recapitulate the spectrum of GBM cellular states, hindering elucidation of the underlying transcriptional regulation of these states. Using our glioblastoma cerebral organoid model, we profiled the chromatin accessibility of 28,040 single cells in five patient-derived glioma stem cell lines. Integration of paired epigenomes and transcriptomes within the context of tumor-normal host cell interactions was used to probe the gene-regulatory networks underlying individual GBM cellular states in a way not readily possible in other in vitro models. These analyses identified the epigenetic underpinnings of GBM cellular states and characterized dynamic chromatin changes reminiscent of early neural development that underlie GBM cell state transitions. Despite large differences between tumors, a shared cellular compartment made up of neural progenitor-like cells and outer radial glia–like cells was observed. Together, these results shed light on the transcriptional regulation program in GBM and offer novel therapeutic targets across a broad range of genetically heterogenous GBMs. Significance: Single-cell analyses elucidate the chromatin landscape and transcriptional regulation of glioblastoma cellular states and identify a radial glia–like population, providing potential targets to disrupt cell states and improve therapeutic efficacy.

PurposeWe hypothesized that an intervention designed to create girl-friendly drug shops would increase access to sexual and reproductive health products and services among adolescent girls and young women (AGYW) (ages 15-24 years) in Tanzania.MethodsWe conducted a four-month randomized trial at 20 drug shops in Shinyanga, Tanzania from August-December 2019 to determine if the Malkia Klabu ("Queen Club") intervention increased AGYW patronage and the provision of HIV self-testing (HIVST), contraception, and health facility referrals to AGYW (primary outcomes). Drug shops were randomized 1:1 to the intervention or comparison arm. All shops were provided with OraQuick HIVST kits to give to AGYW for free. Intervention shops implemented Malkia Klabu, a loyalty program for AGYW created using human-centered design through which AGYW could also access free contraception. We compared outcomes in intention-to-treat analyses using shop observations and shopkeeper records.ResultsBy endline, shops implementing Malkia Klabu had higher AGYW patronage than comparison shops (rate ratio: 4.4; 95% confidence interval: 2.0, 9.8). Intervention shops distributed more HIVST kits (median per shop: 130.5 vs. 58.5, P= .02) and contraceptives (325.5 vs. 7.0, P < .01) to AGYW and provided more referrals for HIV, family planning, or pregnancy services combined (3.5 vs. 0.5, P= .02) than comparison shops.DiscussionThe Malkia Klabu intervention increased AGYW patronage and the provision of HIVST kits, contraception, and referrals to AGYW at drug shops, despite HIVST kits being freely available at all participating shops. Enhancing drug shops with girl-friendly services may be an effective strategy to reach AGYW with sexual and reproductive health services.

Serpentinization-influenced hydrothermal systems, such as the Lost City Hydrothermal Field (LCHF), are considered as potential sites for the origin of life. Despite an abundance of reducing power in this system (H2 and CH4), microbial habitability may be limited by high pH, elevated temperatures, and/or low concentrations of bioavailable carbon. At the LCHF, the relative contribution of biotic and abiotic processes to the vent fluid composition, especially in the lower temperature vents, remain poorly constrained. We present fluid chemistry and isotope data that suggest that all LCHF fluids are derived from a single endmember produced in the hotter, deeper subsurface essentially in the absence of microbial activity. The strontium isotope composition (87Sr/86Sr) of this fluid records the influence of underlying mantle and/or gabbroic rocks, whereas sulfur isotope composition indicates closed-system thermochemical sulfate reduction. Conductive cooling and transport is accompanied by continued sulfate reduction, likely microbial, and mixing with unaltered seawater, which produce second-order vents characterized by higher δ34Ssulfide and lower δ34Ssulfate values. Third-order vent fluids are produced by varying degrees of subsurface mixing between the first- and second-order fluids and a seawater-dominated fluid. Additional biotic and abiotic processes along different flow paths are needed to explain the spatial variability among the vents. Relationships between sulfur geochemistry and hydrogen concentrations dominantly reflect variations in temperature and/or distance from the primary outflow path. Methane concentrations are constant across the field which point to an origin independent of flow path and venting temperature. At Lost City, not all vent fluids appear to have zero Mg concentrations. Thus, we propose an extrapolation to a Sr isotope-endmember composition as an alternative method to estimate endmember fluid compositions at least in similar systems where a two-component mixing with respect to Sr isotopes between seawater and endmember fluids can be established., Geochimica et Cosmochimica Acta, 332, ISSN:0016-7037, ISSN:1872-9533

Eating last is a gendered cultural norm in which the youngest daughters-in-law are expected to eat last after serving others in the household, including men and in-laws. Using women's eating last as an indicator of women's status, we studied the association between eating last and women's mental health. Using four rounds of prospective cohort data of 18-25-year-old newly married women (n = 200) cohabiting with mothers-in-law between 2018 and 2020 in the Nawalparasi district of Nepal, we examined the association between women eating last and depressive symptom severity (measured using 15-item Hopkins Symptom Checklist for Depression; HSCL-D). Twenty-fivepercent of women reported eating last always. The prevalence of probable depression using the established cutoff was 5.5%, consistent with the prevalence of depression in the general population. Using a hierarchical mixed-effects linear regression model, we found that women who always ate last had an expected depressive symptom severity (0-3 on HSCL-D) 0.24 points (95% confidence interval [CI]: 0.13-0.36) greater compared to women who did not eat last when adjusted for demographic variables, household food insecurity, and secular trends. Sensitivity analysis using logistic regression also suggested that women who eat last have greater odds of having probable depression (adjusted odds ratio [AOR] = 4.05; 95% CI: 1.32-12.44). We explored if the association between eating last and depressive symptom severity was moderated by household food insecurity and did not observe evidence of moderation, underscoring the significance of eating last as a woman's status indicator. Our study findings highlight that newly young married women in Nepal are a vulnerable group.

En esta contribución me propongo, en primer lugar, recopilar y ordenar lo que recoge la bibliografía que me ha precedido añadiendo al dossier tradicional algunos hijos y madres aparecidos últimamente, y otros totalmente nuevos, gracias a investigaciones en archivo. En segundo lugar, analizar la categoría de las amantes, cuando están presentes ‒ a la vez que las esposas o no‒ , el trato que reciben en vida del monarca y después de su muerte, así como el comportamiento con los respectivos hijos. Finalmente, se considerarán varios casos relativos al reconocimiento de la condición de hijo de rey, situaciones que se dieron una vez muerto el padre.

Carbonate clumped isotope thermometry, based on the temperature-dependence of clumping of 13C and 18O in the carbonate molecule (Δ47) is a promising tool for paleoclimate reconstruction. In the last few years many discrepancies among Δ47-temperature calibrations have been resolved across the range of relevant paleoclimate temperatures (Meinicke et al., 2020; Anderson et al., 2021). However, there might be other environmental effects on biogenic carbonates from parameters such as the pCO2 and growth rates of the organisms that are still unresolved. We provide a new assessment of the temperature dependence of clumped isotopes in laboratory grown biogenic carbonate at well-constrained experimental conditions, with results from three species of coccolithophores across a growth temperature range of 6-27°C. The three cultured species cover a range of growth rates, growth conditions and species-specific carbon and oxygen vital effects. Because variations in pCO2 and media carbon chemistry are known to trigger vital effects in carbon and oxygen isotopes in coccoliths, we decoupled the temperature solubility effect on CO2 by manipulating culture CO2 independently. Three pCO2 levels at reduced, present day and elevated levels; 200, 400 and 1000 ppm respectively, were kept constant for at least two different temperatures through a continuous culturing set-up. Our new multi-parameter comparison, using updated standardization approaches, provides a critical test of previous conclusions (Katz et al., 2017) that coccolithophore clumped isotopes show little to no vital effects and are close to abiotic equilibrium. Thus, we have performed the first calibration of coccolith calcite and clumped isotopes combining different temperature and pCO2 conditions.References:Anderson, N. T., J. R. Kelson, S. Kele, M. Daëron, M. Bonifacie, J. Horita, T. J. Mackey, et al. 2021. "A Unified Clumped Isotope Thermometer Calibration (0.5–1,100°C) Using Carbonate‐Based Standardization." Geophysical Research Letters 48 (7).Katz, A., M. Bonifacie, M. Hermoso, P. Cartigny, D. Calmels. 2017. “Laboratory-grown coccoliths exhibit no vital effect in clumped isotope (Δ47) composition on a range of geologically relevant temperatures.” Geochimica et Cosmochimica Acta 208: 335-353.Meinicke, N., S.L. Ho, B. Hannisdal, D. Nürnberg, A. Tripati, R. Schiebel, and A.N. Meckler. 2020. "A robust calibration of the clumped isotopes to temperature relationship for foraminifers." Geochimica et Cosmochimica Acta 270: 160-183.

Methane clumped isotope thermometry relies on accurate measurements of relative abundances of the doubly-substituted isotopologues 12CH2D2 and 13CH3D. Calibration of the thermometer requires, regardless of the applied technique, i.e., laser absorption spectroscopy or high-resolution mass spectrometry, routine preparation of thermally re-equilibrated samples spanning the temperature and bulk isotopic composition (δ13C-, δD-CH4) range of the target applications.Here we present a practical method for methane isotopologue re-equilibration over activated γ-Al2O3. We demonstrate complete and reproducible re-equilibration of clumped isotope signatures with minimal alteration of the bulk isotope composition, almost complete sample recovery, and no detectable formation of decomposition products. Samples spanning a range in δD-CH4 of 100 ‰ were equilibrated between 100 °C and 500 °C and used to calibrate a high-resolution quantum cascade laser absorption spectrometer. In addition, we report on a comparison between the spectroscopic measurements carried out at Empa and an independently calibrated high-resolution mass spectrometric technique using a Thermo MAT253 Ultra at IMAU, Utrecht University.This study is supported by the European Commission under the Horizon 2020 – Research and Innovation Framework Programme, H2020-INFRAIA-2020-1 (grant no. 101008004) and the Swiss National Science Foundation project no. 200021_200977.

Supplementary Table (Table S1) and Figure Legends

Supplementary Figures (Figures S1-S5)

The tumor microenvironment is necessary for recapitulating the intratumoral heterogeneity and cell state plasticity found in human primary glioblastoma (GBM). Conventional models do not accurately recapitulate the spectrum of GBM cellular states, hindering elucidation of the underlying transcriptional regulation of these states. Using our glioblastoma cerebral organoid model, we profiled the chromatin accessibility of 28,040 single cells in five patient-derived glioma stem cell lines. Integration of paired epigenomes and transcriptomes within the context of tumor-normal host cell interactions was used to probe the gene-regulatory networks underlying individual GBM cellular states in a way not readily possible in other in vitro models. These analyses identified the epigenetic underpinnings of GBM cellular states and characterized dynamic chromatin changes reminiscent of early neural development that underlie GBM cell state transitions. Despite large differences between tumors, a shared cellular compartment made up of neural progenitor-like cells and outer radial glia–like cells was observed. Together, these results shed light on the transcriptional regulation program in GBM and offer novel therapeutic targets across a broad range of genetically heterogenous GBMs.Significance:Single-cell analyses elucidate the chromatin landscape and transcriptional regulation of glioblastoma cellular states and identify a radial glia–like population, providing potential targets to disrupt cell states and improve therapeutic efficacy.

ObjectivesWe aim to quantify shifts in hospitalisation and mortality and how those were related to the first three phases of the epidemic and individuals’ demographics and health profile among those with a positive test for SARS-CoV-2 treated at the Mexican Social Security Institute’s facilities from March 2020 to October 2021.DesignRetrospective observational study using interrupted time series analysis to identify changes in hospitalisation rate and case fatality rate (CFR) by epidemic wave.SettingData from the Mexican Institute of Social Security’s (IMSS) Online Influenza Epidemiological Surveillance System (SINOLAVE) that include all individuals that sought care at IMSS facilities all over Mexico.ParticipantsAll individuals included in the SINOLAVE with a positive PCR or rapid test for SARS-CoV-2.Primary and secondary outcome measuresMonthly test positivity rates, hospitalisation rates, CFRs and prevalence of relevant comorbidities by age group.ResultsFrom March 2020 to October 2021, the CFR declined between 1% and 3.5%; the declines were significant for those 0–9, 20–29, 30–39, 40–49 and 70 and older. The decline was steep during the first wave and was less steep or was temporarily reversed at the beginning of the second and third waves (changes in the trend of about 0.3% and 3.8%, and between 0.7% and 3.8%, respectively, for some age groups), but then continued to the end of the analytical period. Prevalence of diabetes, hypertension and obesity among patients testing positive also declined—two for most age groups (reductions of up to 10 percentage points for diabetes, 12 percentage points for hypertension and 19 percentage points for obesity).ConclusionData suggest that the decrease in COVID-19 fatality rate is at least partially explained by a change in the profile of those contracting the disease, that is, a falling proportion of individuals with comorbidities across all age groups.

The Lost City hydrothermal field (LCHF) is considered an analogue of Archean alkaline hydrothermal vents where life on Earth may have spawned. Although Lost City was discovered more than 20 years ago, it remains unclear to what extent microbes are involved in the precipitation of the various minerals constituting the hydrothermal chimneys. Most chimneys preserve flow textures comprised of mineral walls bounding paleo-channels, which are preserved in inactive vent structures to a varying degree. Brucite lines the internal part of these channels, while aragonite dominates the exterior. Calcite is also present locally, mostly associated with brucite. Based on a combination of microscopic and geochemical analyses, we interpret brucite, calcite, and aragonite as primary minerals that precipitate abiotically from mixing seawater and hydrothermal fluids. We observe local brucite precipitation on microbial filaments and, in some cases, microbial filaments may affect the growth direction of brucite crystals. The link between brucite and organic compounds is further confirmed by fluorescence microscopy: brucite shows a strong fluorescence not observed in calcite and aragonite. Our results point to brucite as an important link to microbial life in alkaline fluids and is potentially a key aspect for future research on the origin of life.

Carbonate-brucite chimneys are a characteristic of low- to moderate-temperature, ultramafic-hosted alkaline hydrothermal systems, such as the Lost City hydrothermal field located on the Atlantis Massif at 30°N near the Mid-Atlantic Ridge. These chimneys form as a result of mixing between warm, serpentinization-derived vent fluids and cold seawater. Previous work has documented the evolution in mineralogy and geochemistry associated with the aging of the chimneys as hydrothermal activity wanes. However, little is known about spatial heterogeneities within and among actively venting chimneys. New mineralogical and geochemical data (87Sr/86Sr and stable C, O, and clumped isotope) indicate that brucite and calcite precipitate at elevated temperatures in vent fluid-dominated domains in the interior of chimneys. Exterior zones dominated by seawater are brucite-poor and aragonite is the main carbonate mineral. Carbonates form mostly out of oxygen and clumped isotope equilibrium due to rapid precipitation upon vent fluid-seawater mixing. In contrast, the carbonates precipitate close to carbon isotope equilibrium, with dissolved inorganic carbon in seawater as the dominant carbon source, and have δ13C values within the range of marine carbonates. Our data suggest that calcite is a primary mineral in the active hydrothermal chimneys and does not exclusively form as a replacement of aragonite during later alteration with seawater. Elevated formation temperatures and lower 87Sr/86Sr relative to aragonite in the same sample suggest that calcite may be the first carbonate mineral to precipitate.

Supplementary figures and tables with Figure legends.

Preprints enable new forms of peer review that have the potential to be more thorough, inclusive, and collegial. In December 2022, 80 researchers and representatives of funders, institutions, preprint servers, journals, indexers, and review services were invited to gather online and at the Janelia Research Campus for a workshop on Recognizing Preprint Peer Review. Sponsored by HHMI, ASAPbio, and EMBO, this meeting aimed to catalyze community consensus and support for preprint peer review and to create model funder, institutional, and journal policies that recognize both preprints with reviews, and reviews of preprints. Here, we make a call to action to stakeholders in the community to help capture the growing momentum of preprint sharing and empower researchers to provide open and constructive peer review for preprints.

Glioblastoma (GBM), an incurable tumor, remains difficult to model and more importantly to treat due to its genetic/epigenetic heterogeneity and plasticity across cellular states. The ability of current tumor models to recapitulate the cellular states found in primary tumors remains unexplored. To address this issue, we compared single-cell RNA sequencing of tumor cells from 5 patients across four patient-specific glioblastoma stem cell (GSC)–derived model types, including glioma spheres, tumor organoids, glioblastoma cerebral organoids (GLICO), and patient-derived xenografts. We find that GSCs within the GLICO model are enriched for a neural progenitor–like cell subpopulation and recapitulate the cellular states and their plasticity found in the corresponding primary parental tumors. These data demonstrate how the contribution of a neuroanatomically accurate human microenvironment is critical and sufficient for recapitulating the cellular states found in human primary GBMs, a principle that may likely apply to other tumor models.Significance:It has been unclear how well different patient-derived GBM models are able to recreate the full heterogeneity of primary tumors. Here, we provide a complete transcriptomic characterization of the major model types. We show that the microenvironment is crucial for recapitulating GSC cellular states, highlighting the importance of tumor–host cell interactions.See related commentary by Luo and Weiss, p. 907.This article is highlighted in the In This Issue feature, p. 890

CT-PET scan showing clinical response of Pt#2.

Supplementary Table I: IFN-DC release criteria and median values registered among patient-derived IFN-DC (min-max range); Supplementary Table 2: Patients MHC-I and MHC-II alleles and IGHV epitope sequences

Purpose:This study was aimed at evaluating the feasibility, safety, immunologic and clinical responses in patients with follicular lymphoma treated with monocyte-derived dendritic cells generated in the presence of IFNα and GM-CSF (IFN-DC) in combination with low doses of rituximab.Patients and Methods:Firstly, we analyzed in vitro and in vivo the immunologic properties of IFN-DC against follicular lymphoma. Thus, we performed a phase I trial in 8 patients with refractory and relapsed follicular lymphoma based on sequential intranodal injections of low-dose of rituximab and unloaded IFN-DC and report the safety, clinical, and immunologic results of the enrolled patients.Results:Preclinical studies indicated that IFN-DC can synergize with rituximab leading to increased cytotoxicity and T-cell tumor infiltration. The clinical evaluation showed that the combined treatment was totally safe. The overall response rate was 50%, PET-negative complete response rate 37%, and remission is still ongoing in 2/4 of responding patients (median follow-up 26 months, range 11–47). Notably, following the combined therapy all patients showed induction/enhancement of T-cell responses by CD107 degranulation or IFNγ ELISPOT assay against patient-specific tumor IGHV sequences.Conclusions:These results represent the proof-of-principle on the effectiveness of unloaded IFN-DC in inducing durable clinical responses and promoting induction of tumor-specific peripheral T cells, thus suggesting the occurrence of an effective endogenous antitumor vaccination. The overall findings indicate that some unique properties of IFN-DC can be successfully exploited to induce/enhance antitumor responses, thus representing a valuable antitumor strategy for novel and more effective combination therapies in patients with cancer.

CT-PET scan showing clinical response of Pt#3

En esta contribución se pretende, en primer lugar, recopilar y ordenar lo que recoge la bibliografía que me ha precedido; el análisis de nuevas fuentes ha permitido añadir al dosier tradicional otras relaciones e hijos de los reyes hasta ahora totalmente desconocidos. En segundo lugar, analizar la categoría de las amantes, cuándo son presentes —si en contemporaneidad a las esposas o no—, el trato que reciben en vida del monarca y después de su muerte, así como el comportamiento con los respectivos hijos.

BackgroundTimely monitoring of SARS-CoV-2 variants is crucial to effectively managing both prevention and treatment efforts. In this paper, we aim to describe demographic and clinical patterns of individuals with COVID-19-like symptoms during the first three epidemic waves in Mexico to identify changes in those patterns that may reflect differences determined by virus variants.MethodsWe conducted a descriptive analysis of a large database containing records for all individuals who sought care at the Mexican Social Security Institute (IMSS) due to COVID-19-like symptoms from March 2020 to October 2021 (4.48 million records). We described the clinical and demographic profile of individuals tested (3.38 million, 32% with PCR and 68% with rapid test) by test result (positives and negatives) and untested, and among those tested, and the changes in those profiles across the first three epidemic waves.ResultsIndividuals with COVID-19-like symptoms were older in the first wave and younger in the third one (the mean age for those positive was 46.6 in the first wave and 36.1 in the third wave; for negatives and not-tested, the mean age was 41 and 38.5 in the first wave and 34.3 and 33.5 in the third wave). As the pandemic progressed, an increasing number of individuals sought care for suspected COVID-19. The positivity rate decreased over time but remained well over the recommended 5%. The pattern of presenting symptoms changed over time, with some of those symptoms decreasing over time (dyspnea 40.6 to 14.0%, cough 80.4 to 76.2%, fever 77.5 to 65.2%, headache 80.3 to 78.5%), and some increasing (odynophagia 48.7 to 58.5%, rhinorrhea 28.6 to 47.5%, anosmia 11.8 to 23.2%, dysgeusia 11.2 to 23.2%).ConclusionDuring epidemic surges, the general consensus was that any individual presenting with respiratory symptoms was a suspected COVID-19 case. However, symptoms and signs are dynamic, with clinical patterns changing not only with the evolution of the virus but also with demographic changes in the affected population. A better understanding of these changing patterns is needed to improve preparedness for future surges and pandemics.

Reliable temperature reconstructions are necessary to improve climate reconstructions and comparisons with paleoclimate model simulations. Most existing paleotemperature proxies are based on organic and inorganic remains of marine organisms. Despite the evidence that the habitat depth of coccolithophores and other phytoplankton depend on their ability to balance light, nutrients, and grazing pressure, calibrations of proxies based on photosynthesizers often assume they live in the surface ocean. Here we present the first globally distributed dataset of core top multi-species coccolith clumped isotopes (∆47), which show a clear latitudinal thermal gradient and demonstrate coccolith ∆47 sensitivity to temperature. The application of the most recent ∆47-temperature calibration for marine biogenic carbonates yield calcification temperatures implying deep habitats for tropical coccolithophores (from ~50 to up to ~150 m), which could photosynthesize with 1-10% of surface photosynthetic active radiation (PAR) levels. Given the low upper ocean temperature gradient of well-mixed high-latitude locations and the current uncertainties of ∆47 thermometry, coccolith ∆47 cannot be used to reliably constrain a specific habitat depth in these locations. Nevertheless, they are a good indicator of paleotemperatures of the mixed layer. We also use coccolith ∆47 to derive the first regression relating core top coccolith ∆47 and sea surface temperatures (SST). Although this formulation cannot be considered a proper coccolith-specific ∆47 calibration, since it ignores coccolithophore’s potential for calcification at depth, it facilitates comparison with temperature proxies like UK37', which are regressed to SST, rather than production temperature.

BackgroundCOVID-19 would kill fewer people if health programs can predict who is at higher risk of mortality because resources can be targeted to protect those people from infection. We predict mortality in a very large population in Mexico with machine learning using demographic variables and pre-existing conditions.MethodsWe conducted a population-based cohort study with over 1.4 million laboratory-confirmed COVID-19 patients using the Mexican social security database. Analysis is performed on data from March 2020 to November 2021 and over three phases: (1) from March to October in 2020, (2) from November 2020 to March 2021, and (3) from April to November 2021. We predict mortality using an ensemble machine learning method,super learner, and independently estimate the adjusted mortality relative risk of each pre-existing condition using targeted maximum likelihood estimation.ResultsSuper learner fit has a high predictive performance (C-statistic: 0.907), where age is the most predictive factor for mortality. After adjusting for demographic factors, renal disease, hypertension, diabetes, and obesity are the most impactful pre-existing conditions. Phase analysis shows that the adjusted mortality risk decreased over time while relative risk increased for each pre-existing condition.ConclusionsWhile age is the most important predictor of mortality, younger individuals with hypertension, diabetes and obesity are at comparable mortality risk as individuals who are 20 years older without any of the three conditions. Our model can be continuously updated to identify individuals who should most be protected against infection as the pandemic evolves.Key messagesWhat is already known on this topicStudies for Mexico and other countries have suggested that pre-existing conditions such as renal disease, diabetes, hypertension, and obesity are strongly associated with COVID-19 mortality. While age and the presence of pre-existing conditions have been shown to predict mortality, other studies have typically used less powerful statistical approaches, have had smaller sample sizes, and have not been able to describe changes over time.What this study addsThis study examines mortality risk in a very large population (> 60 M); it uses powerful ensemble machine learning methods that outperform regression analyses; and it demonstrates marked changes over time in the degree to which different risk factors predict mortality.How this study might affect research, practice or policyBecause we show an important improvement in predictive performance over traditional regression analyses, and the ability to update estimates as the pandemic evolves, we argue that these methods should be much more widely used to inform national programming in Mexico and elsewhere. Programs that assume that predictive models don’t change over time as variants emerge and as pre-existing immunity evolves due to vaccination and prior infection will not accurately predict mortality risk.

International audience; The Jiangmen Underground Neutrino Observatory (JUNO), the first multi-kton liquid scintillator detector, which is under construction in China, will have a unique potential to perform a real-time measurement of solar neutrinos well below the few MeV threshold typical for Water Cherenkov detectors. JUNO's large target mass and excellent energy resolution are prerequisites for reaching unprecedented levels of precision. In this paper, we provide estimation of the JUNO sensitivity to 7Be, pep, and CNO solar neutrinos that can be obtained via a spectral analysis above the 0.45 MeV threshold. This study is performed assuming different scenarios of the liquid scintillator radiopurity, ranging from the most opti mistic one corresponding to the radiopurity levels obtained by the Borexino experiment, up to the minimum requirements needed to perform the neutrino mass ordering determination with reactor antineutrinos - the main goal of JUNO. Our study shows that in most scenarios, JUNO will be able to improve the current best measurements on 7Be, pep, and CNO solar neutrino fluxes. We also perform a study on the JUNO capability to detect periodical time variations in the solar neutrino flux, such as the day-night modulation induced by neutrino flavor regeneration in Earth, and the modulations induced by temperature changes driven by helioseismic waves.

Safety-critical infrastructures must operate in a safe and reliable way. Fault tree analysis is a widespread method used for risk assessment of these systems: fault trees (FTs) are required by, e.g., the Federal Aviation Administration and the Nuclear Regulatory Commission. In spite of their popularity, little work has been done on formulating structural queries about FT and analyzing these, e.g., when evaluating potential scenarios, and to give practitioners instruments to formulate queries on FTs in an understandable yet powerful way. In this paper, we aim to fill this gap by extending BFL [32], a logic that reasons about Boolean FTs. To do so, we introduce a Probabilistic Fault tree Logic (PFL). PFL is a simple, yet expressive logic that supports easier formulation of complex scenarios and specification of FT properties that comprise probabilities. Alongside PFL, we present LangPFL, a domain specific language to further ease property specification. We showcase PFL and LangPFL by applying them to a COVID-19 related FT and to a FT for an oil/gas pipeline. Finally, we present theory and model checking algorithms based on binary decision diagrams (BDDs)., Comment: arXiv admin note: text overlap with arXiv:2208.13424

Ikaite and pseudomorphs thereafter (“glendonites”) are a potentially powerful tool for palaeoclimatic studies, as a low-temperature proxy. However, much uncertainty still surrounds the drivers of ikaite formation, in particular prerequisite thermal and chemical conditions. Furthermore, the ikaite toglendonite transformation is not fully understood, and it was unclear which calcite phases in glendonites were ikaite-derived and which were later diagenetic calcites. This leads to difficulties in choosing which phase to analyse in order to reconstruct the original ikaite growth environmental conditions. Petrographicexamination of air-transformed ikaite from the Isatkoak Lagoon in Utqiaġvik, Alaska, confirms that both ’Type I’ and ’Type II’ calcite phases seen in glendonites are directly derived from ikaite breakdown and not from secondary sources. Clumped isotope temperature reconstructions for transformed ikaites from Utqiaġvik, and comparison to Recent glendonites from the White Sea, Russia, confirm that clumped isotope thermometry may be used to reconstruct ikaite growth temperatures, whilst stable isotopes and minor elemental analysis reveal that a range of geochemical conditions characterise ikaite growth sites

The European physical journal / C 82(12), 1168 (2022). doi:10.1140/epjc/s10052-022-11002-8, Published by Springer, Heidelberg

Resonant stimulated X-ray Raman spectroscopy of the bimetallic [MnIIIMnIV(μ-O)2(μ-OAC)(tacn)2]2+ manganese complex is investigated in a simulation study. Essential biological processes, including water oxidation in photosynthesis, involve charge transfer between manganese sites of different oxidation states. We study a prototypical binuclear mixed-valence transition-metal complex with two Mn atoms in different oxidation states surrounded by ligand structures and employ a pump-probe sequence of resonant X-ray Raman excitations to follow the charge transfer occurring in the molecule. This allows us to generate and monitor valence-electron wave packets at selected regions in the molecule by exploiting element-specific core-excited states. A two-color protocol is presented, with pump and probe pulses tuned to the Mn and N K-edges. A natural orbital decomposition allows the visualization of the electron dynamics underlying the signal.

Despite a high prevalence in the pediatric trauma population, there remains a lack of large population-based epidemiological studies on pediatric pelvic fractures. Using a de-identified national clinical registry, we investigated the epidemiological features of pediatric pelvic fractures. We performed a retrospective analysis of data obtained from the IBM Watson Health Explorys Platform (Armonk, NY). From all children ages 0-14, two cohorts were created, children diagnosed with a traumatic injury and children diagnosed with a fracture of the pelvis. We then calculated the overall incidence of pelvic fractures, mortality rate, and identified common associated injuries, fracture locations, and complications. 2,690 pediatric pelvic fractures were identified yielding an incidence of 9.8/100,000 children per year with a mortality rate of 0.3%. Pelvic fractures were more common among Caucasians than in African Americans and Asians, and more common in males than females. The most common types of pelvic fracture were fractures of the ilium (42%), pubis (18%), sacrum (11%), ischium (10%), and acetabulum (8%). Most common associated injuries included injury of the lower extremity (43%), intracranial injury (16%), chest injury (13%), injury of the abdomen (9%), and urogenital injury (3%). Rates of common complications associated with malunion were low back pain (10%), acquired leg length discrepancy (1%), and acquired scoliosis (0.3%). The current incidence of pediatric pelvic fracture is 9.8/100,000 children per year with a mortality rate of 0.3%. Further study utilizing large data sets may help to better understand associated injuries, risks of poor outcomes, and optimize treatment strategies.

Background. Timely monitoring of SARS-CoV-2 variants is crucial to effectively managing both prevention and treatment efforts. In this paper, we aim to describe demographic and clinical patterns of individuals suspected of COVID-19 during the first three epidemic waves in Mexico to identify changes in those patterns that may reflect differences determined by virus variants. Methods. We conducted a descriptive analysis of a large database containing records for all individuals who sought care at the Mexican Social Security Institute (IMSS) due to COVID-19-like symptoms from March 2020 to October 2021 (4.48 million records). We described the clinical and demographic profile of individuals tested and untested, and among those tested, those with positive and negative results, and the changes in those profiles across the first three epidemic waves. Results. Individuals with COVID-19-like symptoms were older in the first wave and younger in the third one. As the pandemic progressed, an increasing number of individuals sought care for suspected COVID-19. The positivity rate decreased over time but remained well over the recommended 5%. The pattern of presenting symptoms changed over time, with some decreasing over time (dyspnea 40.6% to 14.0%, cough 80.4% to 76.2%--, fever 77.5% to 65.2%, headache 80.3% to 78.5%), and some increasing (odynophagia 48.7% to 58.5%, rhinorrhea 28.6% to 47.5%, anosmia 11.8% to 23.2%, dysgeusia 11.2% to 23.2%). Conclusion. During epidemic surges, the general consensus was that any individual presenting with respiratory symptoms was very likely to be a COVID-19 case. However, symptoms and signs are dynamic, with clinical patterns changing not only with the evolution of the virus but also with demographic changes in the affected population. A better understanding of these changing patterns is needed to improve preparedness for future surges and pandemics.

The number of older adults (age fifty-five or older) incarcerated in US prisons reached an all-time high just as COVID-19 entered correctional facilities in 2020. However, little is known about COVID-19's impact on incarcerated older adults. We compared COVID-19 outcomes between older and younger adults in California state prisons from March 1, 2020, to October 9, 2021. Adjusted odds ratios (aORs) revealed an increasing risk for adverse COVID-19 outcomes among older age groups (ages 55-64, 65-74, and 75 or older) compared with younger adults, including for documented infection (aOR, 1.3, 1.4, and 1.4, respectively) and hospitalization with COVID-19 (aOR, 4.6, 8.7, and 15.1, respectively). Moreover, although accounting for 17.3percent of the California state prison population, older adults represented 85.8percent of this population's COVID-19-related deaths. Yet a smaller percentage of older adults than younger adults were released from prison during the pandemic. The differential rates of morbidity and mortality experienced by incarcerated older adults should be considered in future pandemic response strategies regarding prisons.

Poster presentation

Poster presentation

The explosive outbreaks of COVID-19 seen in congregate settings such as prisons and nursing homes, has highlighted a critical need for effective outbreak prevention and mitigation strategies for these settings. Here we consider how different types of control interventions impact the expected number of symptomatic infections due to outbreaks. Introduction of disease into the resident population from the community is modeled as a stochastic point process coupled to a branching process, while spread between residents is modeled via a deterministic compartmental model that accounts for depletion of susceptible individuals. Control is modeled as a proportional decrease in the number of susceptible residents, the reproduction number, and/or the proportion of symptomatic infections. This permits a range of assumptions about the density dependence of transmission and modes of protection by vaccination, depopulation and other types of control. We find that vaccination or depopulation can have a greater than linear effect on the expected number of cases. For example, assuming a reproduction number of 3.0 with density-dependent transmission, we find that preemptively reducing the size of the susceptible population by 20% reduced overall disease burden by 47%. In some circumstances, it may be possible to reduce the risk and burden of disease outbreaks by optimizing the way a group of residents are apportioned into distinct residential units. The optimal apportionment may be different depending on whether the goal is to reduce the probability of an outbreak occurring, or the expected number of cases from outbreak dynamics. In other circumstances there may be an opportunity to implement reactive disease control measures in which the number of susceptible individuals is rapidly reduced once an outbreak has been detected to occur. Reactive control is most effective when the reproduction number is not too high, and there is minimal delay in implementing control. We highlight the California state prison system as an example for how these findings provide a quantitative framework for understanding disease transmission in congregate settings. Our approach and accompanying interactive website (https://phoebelu.shinyapps.io/DepopulationModels/) provides a quantitative framework to evaluate the potential impact of policy decisions governing infection control in outbreak settings.

Purpose This study aims to characterize the June 2020 COVID-19 outbreak at San Quentin California State Prison and to describe what made San Quentin so vulnerable to uncontrolled transmission. Design/methodology/approach Since its onset, the COVID-19 pandemic has exposed and exacerbated the profound health harms of carceral settings, such that nearly half of state prisons reported COVID-19 infection rates that were four or more times (and up to 15 times) the rate found in the state’s general population. Thus, addressing the public health crises and inequities of carceral settings during a respiratory pandemic requires analyzing the myriad factors shaping them. In this study, we reported observations and findings from environmental risk assessments during visits to San Quentin California State Prison. We complemented our assessments with analyses of administrative data. Findings For future respiratory pathogens that cannot be prevented with effective vaccines, this study argues that outbreaks will no doubt occur again without robust implementation of additional levels of preparedness – improved ventilation, air filtration, decarceration with emergency evacuation planning – alongside addressing the vulnerabilities of carceral settings themselves. Originality/value This study addresses two critical aspects that are insufficiently covered in the literature: how to prepare processes to safely implement emergency epidemic measures when needed, such as potential evacuation, and how to address unique challenges throughout an evolving pandemic for each carceral setting.