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Self-inflicted burns are a relatively uncommon but profound attempt at suicide. Twenty years ago, we first reviewed our experience with self-inflicted burns. With this current study, we sought to determine whether there had been any change in the incidence or outcomes of self-inflicted burns. All burn patients admitted between January 1, 2012, and December 31, 2021, with self-inflicted burns were compared with all other admissions. The frequency of self-inflicted burns and confounding risk factors of patients with self-inflicted burns remained unchanged. A large proportion (87.4 %) of the patients had psychiatric disease. They also had larger burns and higher mortality than accidental burns. Unexpectedly, logistic regression analysis that controlled for age, total percent total body surface area (TBSA) burn, sex, and inhalation injury revealed that those patients with self-inflicted burns had 72 % lower odds of dying than the general population. In conclusion, there has been no improvement in the incidence of self-inflicted burns. They result in very severe injuries, but when age, burn size, gender, and inhalation injury are controlled for, they have at least as good a chance for survival as the general burn population.

The rapid and accurate quantification of peptides is a critical element of modern proteomics that has become increasingly challenging as proteomic data sets grow in size and complexity. We present here FlashLFQ, a computer program for high-speed label-free quantification of peptides and proteins following a search of bottom-up mass spectrometry data. FlashLFQ is approximately an order of magnitude faster than established label-free quantification methods and can quantify data-dependent analysis (DDA) search results from any proteomics search program. It is available as a graphical user interface program, a command line tool, a Docker image, and integrated into the MetaMorpheus search software.

MetaMorpheus is a free and open-source software program dedicated to the comprehensive analysis of proteomic data. In bottom-up proteomics, protein samples are digested into peptides prior to chromatographic separation and tandem mass spectrometric analysis. The resulting fragmentation spectra are subsequently analyzed with search software programs to obtain peptide identifications and infer the presence of proteins in the samples. MetaMorpheus seeks to maximize the information gleaned from proteomic data through the use of (a) mass calibration, (b) post-translational modification discovery, (c) multiple search algorithms, which aid in the analysis of data from traditional, crosslinking, and glycoproteomic experiments, (d) isotope-based or label-free quantification, (e) multi-protease protein inference, and (f) spectral annotation and data visualization capabilities. This protocol provides detailed descriptions of how use MetaMorpheus and how to customize data analysis workflows using MetaMorpheus tasks to meet the specific needs of the user.

PURPOSE Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. METHODS Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. RESULTS There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction ( P = .015). Follow-up analyses found that MAPS ( v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). CONCLUSION MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.

This paper explores a connection between father parenting traits, guilt and shame proneness, moral identity, and physiological responses to moral shame. In this study, participants answered questionnaires and responded to Kohlberg's (1981) moral dilemma. The researcher read scripted feedback that morally shamed the participants, and cortisol levels were measured following this process. The results were analyzed using multiple linear regression. The father's chaos parenting trait was positively related to increases in cortisol during shaming, and the father's coercion parenting trait was negatively related to increases in cortisol during shaming. The father's structure parenting trait was positively related to guilt-negative behavior evaluations and warmth was negatively related to guilt repair. Finally, the father's warmth was negatively related to moral integrity while chaos was positively related. This research provides insight into the complex process of reacting to moral shame.

The Swan Point site in interior Alaska contains a significant multi-component archaeological record dating back to 14,200 cal BP. The site’s radiocarbon (14C) chronology has been presented in scattered publications that mostly focus on specific archaeological periods in Alaska, in particular its terminal Pleistocene components associated with the East Beringian tradition. This paper synthesizes the site’s 14C data and provides sequential Bayesian models for its cultural zones and subzones. The 14C and archaeological record at Swan Point attests that the location was persistently used over the last 14,000 years, even though major changes are evident within regional vegetation and local faunal communities, reflecting long-term trends culminating in Dene-Athabascan history.

Climate models can produce accurate representations of the most important modes of climate variability, but they cannot be expected to follow their observed time evolution. This makes direct comparison of simulated and observed variability difficult and creates uncertainty in estimates of forced change. We investigate the role of three modes of climate variability, the North Atlantic Oscillation, El Niño–Southern Oscillation and the Southern Annular Mode, as pacemakers of climate variability since 1781, evaluating where their evolution masks or enhances forced climate trends. We use particle filter data assimilation to constrain the observed variability in a global climate model without nudging, producing a near-free-running model simulation with the time evolution of these modes similar to those observed. Since the climate model also contains external forcings, these simulations, in combination with model experiments with identical forcing but no assimilation, can be used to compare the forced response to the effect of the three modes assimilated and evaluate the extent to which these are confounded with the forced response. The assimilated model is significantly closer than the “forcing only” simulations to annual temperature and precipitation observations over many regions, in particular the tropics, the North Atlantic and Europe. The results indicate where initialised simulations that track these modes could be expected to show additional skill. Assimilating the three modes cannot explain the large discrepancy previously found between observed and modelled variability in the southern extra-tropics but constraining the El Niño–Southern Oscillation reconciles simulated global cooling with that observed after volcanic eruptions.

Context Primary production on coral reefs varies under changing conditions such as light and nutrient availability. This variation causes changes in basal stable isotopes as photosynthetic and nutrient pathways change. Aims This study provides a preliminary baseline of nitrogen (δ15N) and carbon (δ13C) stable isotope profiles in Symbiodinium and macroalgae at a spatial scale and along a depth gradient around an island. Methods Coral fragments and macroalgae were collected at depths from the surface to 26 m. δ15N and δ13C stable isotope values were assessed for Symbiodinium relative to cell density per surface area. Key results δ15N values showed a uniform nutrient profile across primary producers. However, chlorophyll-a and Symbiodinium density from Montipora stellata had higher concentrations on the southern side of the island. δ15N values of Symbiodinium from Stylophora pistillata and macroalgae did not change with depth. Depth was associated with a significant decrease in Symbiodinium density, and δ13C values in macroalgae. Conclusions We attribute these findings to Symbiodinium from S. pistillata as depth increases, decreasing cell density but maintaining chlorophyll-a concentration to satisfy the coral-host nutrient requirements. Implications This study sets the scene for future, more comprehensive research on detecting carbon and nitrogen stable isotope values on primary producers in coral reefs.

An open question in SN Ia research is where the boundary lies between 'normal' Type Ia supernovae (SNe Ia) that are used in cosmological measurements and those that sit off the Phillips relation. We present the spectroscopic modelling of one such '86G-like' transitional SN Ia, SN 2021rhu, that has recently been employed as a local Hubble Constant calibrator using a tip of the red-giant branch measurement. We detail its modelling from -12 d until maximum brightness using the radiative-transfer spectral-synthesis code tardis. We base our modelling on literature delayed-detonation and deflagration models of Chandrasekhar mass white dwarfs, as well as the double-detonation models of sub-Chandrasekhar mass white dwarfs. We present a new method for 'projecting' abundance profiles to different density profiles for ease of computation. Due to the small velocity extent and low outer densities of the W7 profile, we find it inadequate to reproduce the evolution of SN 2021rhu as it fails to match the high-velocity calcium components. The host extinction of SN 2021rhu is uncertain but we use modelling with and without an extinction correction to set lower and upper limits on the abundances of individual species. Comparing these limits to literature models we conclude that the spectral evolution of SN 2021rhu is also incompatible with double-detonation scenarios, lying more in line with those resulting from the delayed detonation mechanism (although there are some discrepancies, in particular a larger titanium abundance in SN 2021rhu compared to the literature). This suggests that SN 2021rhu is likely a lower luminosity, and hence lower temperature, version of a normal SN Ia., 25 pages, 22 figures, accepted for publication in MNRAS

Farming systems that support locally diverse agricultural production and high levels of biodiversity are in rapid decline, despite evidence of their benefits for climate, environmental health, and food security. Yet, agricultural policies, financial incentives, and market concentration increasingly constrain the viability of diversified farming systems. Here, we present a conceptual framework to identify novel processes that promote the emergence and sustainability of diversified farming systems, using three real-world examples where farming communities have found pathways to diversification despite major structural constraints. By applying our framework to analyze these bright spots in the United States, Brazil, and Malawi, we identify two distinct pathways—network and institutional—to diversification. These pathways emerge through alignment of factors related to social and ecological structure (policies, institutions, and environmental conditions) and agency (values, collective action, and management decisions). We find that, when network and institutional pathways operate in tandem, the potential to scale up diversification across farms and landscapes increases substantially.

Multiprincipal-element alloys are an enabling class of materials owing to their impressive mechanical and oxidation-resistant properties, especially in extreme environments1,2. Here we develop a new oxide-dispersion-strengthened NiCoCr-based alloy using a model-driven alloy design approach and laser-based additive manufacturing. This oxide-dispersion-strengthened alloy, called GRX-810, uses laser powder bed fusion to disperse nanoscale Y2O3 particles throughout the microstructure without the use of resource-intensive processing steps such as mechanical or in situ alloying3,4. We show the successful incorporation and dispersion of nanoscale oxides throughout the GRX-810 build volume via high-resolution characterization of its microstructure. The mechanical results of GRX-810 show a twofold improvement in strength, over 1,000-fold better creep performance and twofold improvement in oxidation resistance compared with the traditional polycrystalline wrought Ni-based alloys used extensively in additive manufacturing at 1,093 °C5,6. The success of this alloy highlights how model-driven alloy designs can provide superior compositions using far fewer resources compared with the ‘trial-and-error’ methods of the past. These results showcase how future alloy development that leverages dispersion strengthening combined with additive manufacturing processing can accelerate the discovery of revolutionary materials.

We present observations from X-ray to mid-infrared wavelengths of the most energetic non-quasar transient ever observed, AT2021lwx. Our data show a single optical brightening by a factor $>100$ to a luminosity of $7\times10^{45}$ erg s$^{-1}$, and a total radiated energy of $1.5\times10^{53}$ erg, both greater than any known optical transient. The decline is smooth and exponential and the ultra-violet - optical spectral energy distribution resembles a black body with temperature $1.2\times10^4$ K. Tentative X-ray detections indicate a secondary mode of emission, while a delayed mid-infrared flare points to the presence of dust surrounding the transient. The spectra are similar to recently discovered optical flares in known active galactic nuclei but lack some characteristic features. The lack of emission for the previous seven years is inconsistent with the short-term, stochastic variability observed in quasars, while the extreme luminosity and long timescale of the transient disfavour the disruption of a single solar-mass star. The luminosity could be generated by the disruption of a much more massive star, but the likelihood of such an event occurring is small. A plausible scenario is the accretion of a giant molecular cloud by a dormant black hole of $10^8 - 10^9$ solar masses. AT2021lwx thus represents an extreme extension of the known scenarios of black hole accretion., 11 pages, 5 figures, Accepted for publication in MNRAS

In eukaryotes, dynamins and dynamin-related proteins (DRPs) are high–molecular weight GTPases responsible for mechanochemical fission of organelles or membranes. Of the six DRP subfamilies in Arabidopsis thaliana, AtDRP1 and AtDRP2 family members serve as endocytic accessory proteins in clathrin-mediated endocytosis. Most studies have focused on AtDRP1A and AtDRP2B as critical modulators of plant pattern-triggered immunity (PTI) against pathogenic, flagellated Pseudomonas syringae pv. tomato DC3000 bacteria and immune signaling in response to the bacterial flagellin peptide flg22. Much less is known about AtDRP2A, the closely related paralog of AtDRP2B. AtDRP2A and AtDRP2B are the only classical, or bona fide, dynamins in Arabidopsis, based on their evolutionary conserved domain structure with mammalian dynamins functioning in endocytosis. AtDRP2B but not AtDRP2A is required for robust ligand-induced endocytosis of the receptor kinase FLAGELLIN SENSING2 for dampening of early flg22 signaling. Here, we utilized Arabidopsis drp2a null mutants to identify AtDRP2A as a positive contributor to effective PTI against P. syringae pv. tomato DC3000 bacteria, consistent with reduced PATHOGEN RELATED1 ( PR1) messenger RNA accumulation. We provide evidence that AtDRP2A is a novel modulator of late flg22 signaling, contributing positively to PR1 gene induction but negatively to polyglucan callose deposition. AtDRP2A has no apparent roles in flg22-elicited mitogen-activated protein kinase defense marker gene induction. In summary, this study adds the evolutionary conserved dynamin AtDRP2A to a small group of vesicular trafficking proteins with roles as non-canonical contributors in immune responses, likely due to modulating one or both the localization and activity of multiple different proteins with distinct contributions to immune signaling. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

A failed graft-versus-tumor (GVT) effect is a common mechanism of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Although targeting the PD-1/PD-L1 axis may restore GVT effects, PD-1 blockade exacerbates graft-versus-host disease (GVHD) in murine models, and severe GVHD can occur in patients treated with anti-PD-1 therapy after alloHCT. Therefore, we developed a prospective study to assess the safety and efficacy of pembrolizumab in patients relapsing after alloHCT. Eligible patients received pembrolizumab (200 mg every 3 weeks) for up to 2 years. Twelve patients were enrolled (8 patients with acute myeloid leukemia, 1 patient with myelodysplastic syndrome, 1 patient with classical Hodgkin lymphoma, and 2 patients with diffuse large B-cell lymphoma [DLBCL]). All participants received reduced-intensity preparative regimens with in vivo T-cell depletion. The median time from alloHCT to enrollment was 587 days (range, 101-4211). Three participants (25%) experienced grade 3 to 4 immune-related adverse events (irAE) (pneumonitis, 2 patients; hyperthyroidism, 1 patient), all occurring after 1 to 2 cycles, and resolving after pembrolizumab discontinuation and corticosteroid treatment. irAEs of any grade occurred in 5 patients (42%). No treatment-emergent GVHD was observed. Overall and complete response (CR) rates were 22% (2/9). Both patients achieving CRs had PD-L1 gene–amplified lymphomas and diffuse PD-L1 expression on pretreatment biopsies. An acquired EZH2 mutation was identified at relapse in a patient with DLBCL who achieved an initial CR to pembrolizumab, which was associated with downregulated HLA expression on malignant B cells, implicating EZH2 mutations as a potential immune escape mechanism after PD-1–blockade therapy. In conclusion, after alloHCT, treatment with pembrolizumab is feasible and associated with objective responses in relapsed lymphoid malignancies but can induce severe irAEs, requiring vigilant monitoring. This trial was registered at www.clinicaltrials.gov as #NCT02981914.