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Highlights • We present a T5 record of the Pb isotope composition Labrador Sea seawater. • These data can be used to track Laurentide Ice Sheet (LIS) extent over Hudson Bay. • LIS retreat during T5 occurred over longer timescales than that for T2 and T1. • LIS deglaciation played important role in protracted nature of T5 sea-level rise. • Ice retreat during T1 may not be applicable template for older terminations in GIA modelling. Termination (T) 5, ∼424 ka, involved the biggest deglaciation of land-ice mass during the Quaternary. Warming and ice-sheet retreat during T5 led to an exceptionally long period of interglacial warmth known as Marine Isotope Stage (MIS) 11, ∼424–395 ka. A detailed understanding of the history of continental ice-sheet decay during T5 is required to disentangle regional contributions of ice-sheet retreat to sea-level rise (that range between ∼1 and 13 m above present day) and to correct it for glacio-isostatic adjustments (GIA). Yet little is known about the timing and magnitude of retreat during this time of the volumetrically most important continental ice sheet in the Northern Hemisphere, the Laurentide Ice Sheet (LIS). Here we present new authigenic Fe-Mn oxyhydroxide-derived high-resolution records of Pb isotope data and associated rare earth element profiles for samples spanning T5 from Labrador Sea IODP Site U1302/3. These records feature astronomically-paced radiogenic Pb isotope excursions that track increases in chemical weathering of North American bedrock and freshwater routing to the Labrador Sea via Hudson Straits associated with LIS retreat. Our records show that LIS retreat during T5 began 429. 2 ± 7.9 ka (2σ) and likely occurred over a longer timescale (by ∼10 to 5 kyr) than that observed for T2 and T1. They also show that Hudson Bay Ice Saddle collapse (and therefore LIS break-up) occurred ∼419 ± 4.7 ka (2σ), around the same time as best estimates of southern Greenland deglaciation, but ∼12 kyr before LIS deglaciation and the sea-level high-stand associated with the latter half of MIS 11 likely occurred. Our findings therefore highlight that ice-mass loss on North America likely played an important role in the seemingly protracted nature of T5 sea-level rise. A comparison of the deglaciation histories of the LIS and the southern Greenland Ice Sheet during T5, T2 and T1 also demonstrates that the well-constrained history of regional ice-sheet retreat during T1 is not always applicable as a template for older late Pleistocene terminations in GIA modelling.

IMPORTANCE: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. OBJECTIVE: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. DESIGN, SETTING, AND PARTICIPANTS: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster’s key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. EXPOSURE: Machine learning consensus clustering approach. MAIN OUTCOMES AND MEASURES: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. RESULTS: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. CONCLUSIONS AND RELEVANCE: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups.

Additional file 2: Appendix 2. Health care providers semi-structured interview guide.

Additional file 1: Appendix 1. PARENT semi-structured interview guide.

Additional file 3.

Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.

Carbon offset programs are critical in the fight against climate change. One emerging threat to the long-term stability and viability of forest carbon offset projects is wildfires, which can release large amounts of carbon and limit the efficacy of associated offsetting credits. However, analysis of wildfire risk to forest carbon projects is challenging because existing models for forecasting long-term fire risk are limited in predictive accuracy. Therefore, we propose an explainable artificial intelligence (XAI) model trained on 7 million global satellite wildfire observations. Validation results suggest substantial potential for high resolution, enhanced accuracy projections of global wildfire risk, and the model outperforms the U.S. National Center for Atmospheric Research's leading fire model. Applied to a collection of 190 global forest carbon projects, we find that fire exposure is projected to increase 55% [37-76%] by 2080 under a mid-range scenario (SSP2-4.5). Our results indicate the large wildfire carbon project damages seen in the past decade are likely to become more frequent as forests become hotter and drier. In response, we hope the model can support wildfire managers, policymakers, and carbon market analysts to preemptively quantify and mitigate long-term permanence risks to forest carbon projects., Comment: 6 pages, 5 figures. Published in ICLR 2023 Workshop: Tackling Climate Change with Machine Learning

There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex $\textbf{Pt1}$ significantly reduces fungal load in an in vivoG. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) of quantitative measures of platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs of pathway-specific functional responses to agonism by adenosine 5'-diphosphate, a glycoprotein VI-specific collagen mimetic, and thrombin receptor-agonist peptides, each specific to 1 of the G protein-coupled receptors PAR-1 and PAR-4, in subsets of 1562 individuals. We identified an association (P = 2.75 × 10-40) between a common intronic variant, rs10886430, in the G protein-coupled receptor kinase 5 gene (GRK5) and the sensitivity of platelets to activate through PAR-1. The variant resides in a megakaryocyte-specific enhancer that is bound by the transcription factors GATA1 and MEIS1. The minor allele (G) is associated with fewer GRK5 transcripts in platelets and the greater sensitivity of platelets to activate through PAR-1. We show that thrombin-mediated activation of human platelets causes binding of GRK5 to PAR-1 and that deletion of the mouse homolog Grk5 enhances thrombin-induced platelet activation sensitivity and increases platelet accumulation at the site of vascular injury. This corroborates evidence that the human G allele of rs10886430 is associated with a greater risk for cardiovascular disease. In summary, by combining the results of pathway-specific GWASs and expression quantitative trait locus studies in humans with the results from platelet function studies in Grk5-/- mice, we obtain evidence that GRK5 regulates the human platelet response to thrombin via the PAR-1 pathway.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

There is a dire need for new compounds to combat antibiotic resistance: metal complexes might provide the solution. 906 metal complexes were evaluated against dangerous ESKAPE pathogens and found to have a higher hit-rate than organic molecules., There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.

This research used samples and/or data provided by the Oman Drilling Project. The Oman Drilling Project (OmanDP) has been possible through co-mingled funds from the International Continental Scientific Drilling Project (ICDP; Peter B. Kelemen, Juerg Matter, Damon A. H. Teagle Lead PIs), the Sloan Foundation -Deep Carbon Observatory (grant no. 2014-3-01, Kelemen PI), the National Science Foundation (grant no. NSF-EAR-1516300, Kelemen lead PI), NASA -Astrobiology Institute (grant no. NNA15BB02A, Templeton PI), the German Research Foundation (DFG: grant no. KO 1723/21-1, Koepke PI), the Japanese Society for the Promotion of Science (JSPS (grant no. 16H06347), Michibayashi PI; and KAKENHI (grant no. 16H02742), Takazawa PI), the European Research Council (Adv: grant no. 669972; Jamveit PI), the Swiss National Science Foundation (SNF: grant no. 20FI21_163073, Fruh-Green PI), JAMSTEC, the TAMU-JR Science Operator, and contributions from the Sultanate of Oman Ministry of Regional Municipalities and Water Resources, the Oman Public Authority of Mining, Sultan Qaboos University, CNRS-Univ. Montpellier, Columbia University of New York, and the University of Southampton. Mathieu Rospabe's participation in on-site and shipboard operations was made possible through a financial support provided by the Centre National de la Recherche Scientifique-Institut National des Sciences de l'Univers (CNRS-INSU), IODP-France (regular fund)., The Oman Drilling Project (OmanDP), performed under the International Continental Scientific Drilling Program (ICDP), is an international scientific research project that undertook drilling at a range of sites in the Semail ophiolite (Oman) to collect core samples spanning the stratigraphy of the ophiolite, from the upper oceanic crust down to the basal thrust. The cores were logged to International Ocean Discovery Program (IODP) standards aboard the D/V Chikyu. During ChikyuOman2018 Leg 3 (July–August 2018), participants described cores from the crust–mantle transition (CM) sites. The main rock types recovered at these sites were gabbros, dunites and harzburgites, rocks typically forming the base of the oceanic crust and the shallow mantle beneath present-day spreading centres. In addition to the core description, selected samples were analysed by X-ray fluorescence spectrometry (XRF) for their chemical compositions, including major, minor and some trace elements. To complement these standard procedures, we developed new approaches to measure ultra-trace element concentrations using a procedure adapted from previous works to prepare fine-grained pressed powder pellets coupled with laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis using instrumentation aboard the D/V Chikyu. First, three (ultra)mafic reference materials were investigated to test and validate our procedure (BHVO-2, BIR-1a and JP-1), and then the procedure was applied to a selection of gabbro and dunite samples from the CM cores to explore the limitations of the method in its current stage of development. The obtained results are in good agreement with preferred values for the reference materials and with subsequent solution replicate analyses of the same samples performed in shore-based laboratories following Leg 3 for the CM samples. We describe this procedure for the determination of 37 minor and (ultra-)trace elements (transition elements and Ga, Li and Large-Ion Lithophile Elements (LILE), Rare Earth Elements (REE), High-Field-Strength Elements (HFSE), U, Th, and Pb) in mafic and ultramafic rocks. The presented method has the major advantage that it allows the determination at sea of the (ultra-)trace element concentrations in a “dry”, safe way, without using acid reagents. Our new approach could be extended for other elements of interest and/or be improved to be adapted to other rock materials during future ocean drilling operations aboard the D/V Chikyu and other platforms., International Continental Scientific Drilling Project (ICDP), Sloan Foundation -Deep Carbon Observatory 2014-3-01, National Science Foundation (NSF) NSF-EAR-1516300, NASA -Astrobiology Institute NNA15BB02A, German Research Foundation (DFG) KO 1723/21-1, Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science 16H06347 Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research (KAKENHI) 16H02742, European Research Council (ERC) European Commission 669972, Swiss National Science Foundation (SNSF) 20FI21_163073, JAMSTEC, TAMU-JR Science Operator, Sultanate of Oman Ministry of Regional Municipalities and Water Resources, Oman Public Authority of Mining, Sultan Qaboos University, CNRS-Univ. Montpellier, Columbia University of New York, University of Southampton, Centre National de la Recherche Scientifique (CNRS), IODP-France (regular fund)

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan-Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50years, p&nbsp

Supplemental material, sj-docx-1-pmj-10.1177_02692163221105599 for Measuring quality of dying, death and end-of-life care for children and young people: A scoping review of available tools by Catriona R Mayland, Katy A Sunderland, Matthew Cooper, Paul Taylor, Philip A Powell, Lucy Zeigler, Vicki Cox, Constance Gilman, Nicola Turner, Kate Flemming and Lorna K Fraser in Palliative Medicine

Additional file 1. Interview question guide parent.

Additional file 4. Semi-structured interview guide for healthcare provider.

Additional file 3. Healthcare provider focus group guide.

There is no standard definition for "HLA incompatible" transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.

Additional file 7. Telephone follow-up at 6-12 weeks post discharge.

Additional file 6. Medical record audit checklist form.

Additional file 5. Semi-structured interview guide for healthcare providers.

Additional file 2. Semi-structured interview guide for healthcare provider.

Additional file 1. Home Exercise Programme.

This paper consists of two parts, namely, “Is the Landscape of the Problem of Evil at an Impasse?” and “A Pragmatic Argument against Reliance in God to Prevent Horrendous Evils.” The first part of this paper completes an analysis of formulations around the problem of evil, analysis of logical and evidential arguments from evil, and analysis of theist responses to the problem of evil. Within the first part, I establish that certain arguments from evil are not valid, so they will not convince the theist. In response to those which are however, the theist does not convince the atheist to abandon the problem of evil. Sceptical theism allows the theist to remain unconvinced by the problem of evil and immune to any evidential argument from evil. Due to colliding atheist and theist principles, there is an impasse in the debate. The second part of this paper aims to take a more pragmatic approach to the problem of evil. Rather than focusing on debate and conjecture within the landscape of the problem of evil, this paper seeks to establish a common idea that theists and atheists will be able to hold. Both atheists and theists seek to eliminate evil. Within the second part of the paper, I establish that reliance in God alone to prevent horrendous evils is an unreasonable action. I do this through an analysis and application of pragmatism and Humean thought to the problem of evil. The application is largely based around naturalist background assumptions which atheists and theists will all hold, and how these assumptions inform us of what actions may be reasonable and unreasonable.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

The coronavirus disease 2019 (COVID‐19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid test (NAT) for COVID‐19 is unclear as this may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of prospective data, transplant professionals at U.S. adult kidney transplant centers were surveyed to determine community practice (N: 92 centers, capturing 40.8% of centers and 56.6% of transplants performed). The majority (96.8%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 31.6% of centers proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with transplant in patients with positive tests due to presumed viral shedding. Furthermore, very few centers are requiring COVID‐19 vaccination prior to transplantation despite early evidence suggesting reduced immunogenicity in transplant patients on immunosuppression. This article is protected by copyright. All rights reserved

Fluorescent probes derived from the fluoroquinolone antibiotic ciprofloxacin were synthesised using a Cu(i)-catalysed azide–alkyne cycloaddition (CuAAC) to link a ciprofloxacin azide derivative with alkyne-substituted green and blue fluorophores., Fluorescent probes derived from the fluoroquinolone antibiotic ciprofloxacin were synthesised using a Cu(i)-catalysed azide–alkyne cycloaddition (CuAAC) to link a ciprofloxacin azide derivative with alkyne-substituted green and blue fluorophores. The azide (2) and fluorophore (3 and 4) derivatives retained antimicrobial activity against Gram-positive and Gram-negative bacteria. The use of confocal fluorescent microscopy showed intracellular penetration, which was substantially enhanced in the presence of carbonyl cyanide 3-chlorophenylhydrazone as an efflux pump inhibitor in Escherichia coli.

The primary task was to create a database in Python, using information from either the United States Patent and Trademark Office or Google Patents, which allows efficient lookups using information such as patent assignee and the patent number. Google Patents was chosen because it contained international patent information rather than being limited to just the United States. The Jupyter Notebook was made to use Beautiful Soup to scrape data from Google Patents. The workflow of the code is to start with a user-defined comma-separated values file that specifies names, e.g., of restaurants and hotel firms, that are relevant to the analysis the user wants to conduct. The first tasks were to read in the query, create a dictionary of company names with associated patent numbers, scrape websites for lxml data, and write raw data to JSON and Excel. The next task was to analyze the stored information qualitatively or quantitatively. Here qualitative analysis was chosen in the form of Natural Language Processing (NLP). The goal was to classify the patents using NLP. The key steps included noise removal, stop word removal, and lemmatization. With this database, we can perform numerous types of analyses to study the effect of patents on the total valuation of companies. It is anticipated that Dr. Zach and future Computer Science students will build upon the current work and conduct additional forms of analysis. The two versions of the final report are in PatentDataAnalysisReport.docx (Word) and PatentDataAnalysisReport.pdf (PDF). The two versions of the final presentation are in PatentDataAnalysisPresentation.odp (OpenDocument Presentation) and PatentDataAnalysisPresentation.pdf (PDF).

Natural Flood Management (NFM) seeks to utilise natural processes within the landscape to reduce flood risk and is increasingly being viewed as a sustainable, cost effective, and complementary addition to flood defence infrastructure. One NFM measure is to increase the proportion of forested lands within catchments draining to the communities at risk. Tree cover has good potential to reduce flood risk by increasing canopy evaporation, enhancing below and above ground flood storage and slowing the flow of water towards streams. However, the extent to which these mechanisms are superior for forestry, compared to other land uses, and how they vary throughout the year and for different forest types remains difficult to predict, which is a major gap in our ability to quantify how forest cover can help reduce flood risk. Here, we present a study that utilises LoRaWAN, a developing wireless sensor network technology, to provide real time collection of canopy interception and streamflow data at the Pennal catchment in Wales, UK. LoRaWAN is an emerging Low Power Wide Area Network (LPWAN) protocol designed for Internet of Things (IoT) applications. The capability of LoRaWAN to operate under harsh attenuation and interference conditions make it well suited to the forest catchment area which is characterised by dense vegetation and varied topography. This study will utilise a network of tipping bucket rain gauges and stream flow monitors distributed in different forest types and densities. The rain gauges and water level monitors are the end devices (IoT things) in the network which perform a direct communication with LoRaWAN Gateways, from which the data is ‘pushed’ to a server for storing and assimilation. The data will be used to develop and validate a coupled canopy and soil hydrology model. This will guide forest management and aid in quantifying the effects of natural flood management techniques, initially within the Pennal catchment, with a view to expanding to the regional scale.

Objective\ud Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD.\ud Method\ud Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM‐IV‐TR criteria on a 4‐point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms. \ud Results\ud The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non‐significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests.\ud Conclusions\ud The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions.

Along with cancer, cardiovascular and cerebrovascular diseases remain by far the most common causes of death. Heart attacks and strokes are diseases in which platelets play a role, through activation on ruptured plaques and subsequent thrombus formation. Most platelet agonists activate platelets via G protein-coupled receptors (GPCRs), which make these receptors ideal targets for many antiplatelet drugs. However, little is known about the mechanisms that provide feedback regulation on GPCRs to limit platelet activation. Emerging evidence from our group and others strongly suggests that GPCR kinases (GRKs) are critical negative regulators during platelet activation and thrombus formation. In this review, we will summarize recent findings on the role of GRKs in platelet biology and how one specific GRK, GRK6, regulates the hemostatic response to vascular injury. Furthermore, we will discuss the potential role of GRKs in thrombotic disorders, such as thrombotic events in COVID-19 patients. Studies on the function of GRKs during platelet activation and thrombus formation have just recently begun, and a better understanding of the role of GRKs in hemostasis and thrombosis will provide a fruitful avenue for understanding the hemostatic response to injury. It may also lead to new therapeutic options for the treatment of thrombotic and cardiovascular disorders.

A critical step in satellite retrievals of trace gas columns is the calculation of the air mass factor (AMF) used to convert observed slant columns to vertical columns. This calculation requires a priori information on the shape of the vertical profile. As a result, comparisons between satellite-retrieved and model-simulated column abundances are influenced by the a priori profile shape. We examine how differences between the shape of the simulated and a priori profiles can impact the interpretation of satellite retrievals by performing an adjoint-based four-dimensional variational (4D-Var) assimilation of synthetic NO2 observations for constraining NOx emissions. We use the GEOS-Chem adjoint model to perform assimilations using a variety of AMFs to examine how a posteriori emission estimates are affected if the AMF is calculated using an a priori shape factor that is inconsistent with the simulated profile. In these tests, an inconsistent a priori shape factor increased root mean square errors in a posteriori emission estimates by up to 30 % for realistic conditions over polluted regions. As the difference between the simulated profile shape and the a priori profile shape increases, so do the corresponding assimilated emission errors. This reveals the importance of using simulated profile information for AMF calculations when comparing that simulated output to satellite-retrieved columns.

A critical step in satellite retrievals of trace gas columns is the calculation of the air mass factor (AMF) used to convert observed slant columns to vertical columns. This calculation requires a priori information on the shape of the vertical profile. As a result, comparisons between satellite-retrieved and model-simulated column abundances are influenced by the a priori profile shape. We examine how differences between the shape of the simulated and a priori profile can impact the interpretation of satellite retrievals by performing an adjoint-based 4D-Var assimilation of synthetic NO2 observations for constraining NOx emissions. We use the GEOS-Chem Adjoint model to perform assimilations using a variety of AMFs to examine how a posteriori emission estimates are affected if the AMF is calculated using an a priori shape factor that is inconsistent with the simulated profile. In these tests, an inconsistent a priori shape factor increased errors in a posteriori emissions estimates by up to 80 % over polluted regions. As the difference between the simulated profile shape and the a priori profile shape increases, so do the corresponding assimilated emission errors. This reveals the importance of using simulated profile information for AMF calculations when comparing that simulated output to satellite retrieved columns.

G protein–coupled receptors (GPCRs) mediate the majority of platelet activation in response to agonists. However, questions remain regarding the mechanisms that provide negative feedback toward activated GPCRs to limit platelet activation and thrombus formation. Here we provide the first evidence that GPCR kinase 6 (GRK6) serves this role in platelets, using GRK6(−/−) mice generated by CRISPR-Cas9 genome editing to examine the consequences of GRK6 knockout on GPCR-dependent signaling. Hemostatic thrombi formed in GRK6(−/−) mice are larger than in wild-type (WT) controls during the early stages of thrombus formation, with a rapid increase in platelet accumulation at the site of injury. GRK6(−/−) platelets have increased platelet activation, but in an agonist-selective manner. Responses to PAR4 agonist or adenosine 5′-diphosphate stimulation in GRK6(−/−) platelets are increased compared with WT littermates, whereas the response to thromboxane A(2) (TxA(2)) is normal. Underlying these changes in GRK6(−/−) platelets is an increase in Ca(2+) mobilization, Akt activation, and granule secretion. Furthermore, deletion of GRK6 in human MEG-01 cells causes an increase in Ca(2+) response and PAR1 surface expression in response to thrombin. Finally, we show that human platelet activation in response to thrombin causes an increase in binding of GRK6 to PAR1, as well as an increase in the phosphorylation of PAR1. Deletion of GRK6 in MEG-01 cells causes a decrease in PAR1 phosphorylation. Taken together, these data show that GRK6 regulates the hemostatic response to injury through PAR- and P2Y(12)-mediated effects, helping to limit the rate of platelet activation during thrombus growth and prevent inappropriate platelet activation.

Additional file 2. STROBE statement. Checklist of reporting guidelines for observational studies (cross-sectional).

Additional file 1. Detailed description of multiple imputation.

We study supercritical $O(d)$-equivariant biharmonic maps with a focus on $d = 5$, where $d$ is the dimension of the domain. We give a characterisation of non-trivial equivariant biharmonic maps from $\mathbf{R}^5$ into $S^5$ as heteroclinic orbits of an associated dynamical system. Moreover, we prove the existence of such non-trivial equivariant biharmonic maps. Finally, in stark contrast to the harmonic map analogue, we show the existence of an equivariant biharmonic map from $B^5(0, 1)$ into $S^5$ that winds around $S^5$ infinitely many times.

For several decades now, the study of environmental impacts on human well-being has been informed by what are called "People and Pixels'' methods: the combining of remotely sensed data about environmental conditions with geolocated data from household surveys about health and nutrition. However, much of this work has been conducted at the scale of individual countries and often relies on only one or two survey waves, which creates substantial issues around spatial autocorrelation and endogeneity. Furthermore, much of this work uses simple linear regression as its analysis technique, which is limited in its ability to describe spatial variation as well as non-linearities in the relationship between the environment and human well-being. Thus, this dissertation uses several insights from the emerging field of data science to advance these methods. First, this analysis draws on large, multinational datasets from dozens of surveys, making it possible to better estimate the non-linear effects of climate extremes on human well-being as well as examine spatial heterogeneities in vulnerability. Secondly, this analysis uses techniques at the boundary between traditional econometric regression models and more complex machine learning models, such as using Generalized Additive Models (GAMs) as well as LASSO estimation. This permits the creation of spatially-varying terms as well as nonlinear effects. Applying these techniques, the dissertation has yielded several insights that could be beneficial to policymakers in governments, non-profits, and multinational organizations. The initial chapters analyze the effects of rainfall anomalies on food security and malnutrition, finding that the effect of an anomaly varies considerably depending on the local socioeconomic and environmental contexts, with low-income, poorly-governed, and arid countries, such as Somalia and Yemen, being the most vulnerable. The latter chapters look at the role of ecosystem services in improving human livelihoods, as well as how land cover is associated with dependence on local provisioning ecosystem services.