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Farther east: new Ghilarellinae wasps (Hymenoptera: Sepulcidae) from the Albian of the Republic of Korea extend the geographic range of the subfamily
Get PDFThe study of the invertebrate fauna of the lower Albian Jinju Formation (Republic of Korea) has experienced renewed interest over the past decade, with numerous new extinct species described each year. Among the various insect orders, Hymenoptera are relatively abundant in the assemblage, with many taxa being discovered and formally described on a regular basis. Within this group, Symphyta are particularly well represented, with series of specimens of varying preservation quality being documented. These newly discovered specimens frequently represent new species belonging to genera already known from subcontemporaneous deposits in China, Mongolia, and Russia, supporting the idea of a relatively homogeneous Early Cretaceous Asian entomofauna. Here, we further corroborate this pattern by describing a new species of Ghilarellinae assigned to the Asian genus Ghilarella, Ghilarella jinjuensis sp. nov. In addition, we describe a second species of the previously monotypic genus Meiaghilarella, which was formerly known only from Spain. The new species, Meiaghilarella stanislawlemi sp. nov., substantially extends the geographic range of the genus during the Albian, from a previously restricted occurrence in Spain to a trans-Laurasian distribution
Propensity-matched analysis of the impact of saphenous vein graft external stenting on clinical outcomes in coronary bypass surgery: The RESTART study
Get PDFObjectiveExternal saphenous vein graft stenting has been shown to reduce intimal hyperplasia, lumen irregularities, and flow disturbances after coronary artery bypass grafting (CABG). The objective of this study is to evaluate the effect of saphenous vein graft external stenting on clinical outcomes up to 5 years.MethodsOutcomes for patients who received external vein graft stenting in an international, real-world cohort were compared in a propensity matched analysis with patients from the Arterial Revascularization Trial (ISRCTN46552265). All eligible patients required an internal mammary artery graft to the left anterior descending coronary artery, received at least one vein graft, and survived to discharge. The primary end point was major adverse cardiovascular and cerebrovascular events at 1 year after surgery, consisting of all-cause mortality, myocardial infarction, repeat revascularization, and cerebrovascular accident. Secondary end points included 5-year major adverse cardiovascular and cerebrovascular events with and without stroke and annualized target vessel revascularization.ResultsIn total, 789 treated and 2205 control patients were included. At 1 year after CABG, the weighted hazard ratio comparing outcomes between treated and control patients was 0.60 (90% confidence interval, 0.38-0.94, P = .03). The benefits associated with external stenting for the composite outcome persisted through 5 years' post-CABG (hazard ratio, 0.70; 95% confidence interval, 0.51-0.98, P = .04). Annual target vessel revascularization rates in vein grafts were significantly lower in the venous external support cohort at 2 to 5 years after surgery (P = .009-.03).ConclusionsThe current study demonstrates that external vein graft stenting is associated with a significantly lower risk of experiencing adverse clinical outcomes up to 5 years after surgery compared with standard of care
Surveillance of Healthcare-Associated Infections in the WHO African Region: Systematic Review of Literature from 2011 to 2024
Get PDFThe Application of Stepwise Pelvic Devascularisation in the Management of Severe Placenta Accreta Spectrum as Part of the Soleymani and Collins Technique for Caesarean Hysterectomy: Surgical Description and Evaluation of Short- and Long-Term Outcomes
Get PDFBackground: Severe (FIGO grade 3b & c) placenta accreta spectrum (PAS) is potentially a life-threatening condition due to catastrophic haemorrhage at delivery. Consequently, interventional radiology (IR) techniques are often employed to prevent massive blood loss, but this is not always readily available, is costly, and can cause significant morbidity, including distal limb ischaemia due to thrombus formation. We believe that internal iliac ligation under direct vision is a safe option to control bleeding. We sought to evaluate the short- and long-term outcomes relating to this technique compared to IR. Methods: This is a mixed-methods cohort study of women with severe PAS who underwent hysterectomy with either surgical devascularisation, as part of the Soleymani and Collins (SAC) technique, or IR insertion of internal iliac balloon catheters, in a UK tertiary referral centre for PAS between 2011 and 2022. Only women with intraoperative diagnosis of very severe PAS (FIGO stage 3b & c) were included in this study. Results: Of the 22 women invited to participate in the long-term component of the study, 59% agreed. Women in the surgical devascularisation group experienced no adverse short or late sequelae related to internal iliac arterial ligation. Pelvic devascularisation (11 patients, 41%) demonstrated a reduction in median estimated blood loss, 1600 millilitres vs. 2500 millilitres in the IR balloon catheter group (p = 0.04). Conclusions: We have demonstrated that the SAC technique for surgical devascularisation is a safe method for achieving haemorrhage control during caesarean hysterectomy for severe PAS. It also appears to be at least as effective at haemorrhage control as IR balloon occlusion of the internal iliac vessels
Low Levels of Mouse γδ T Cell Development Persist in the Presence of Null Mutants of the LAT Adaptor
Get PDFActivation through the T cell receptor (TCR) initiates a signaling cascade in T cells that induces extensive molecular and cellular changes. The adaptor protein Linker for Activation of T cells (LAT) plays an essential role in transducing activation and regulatory signals downstream of the TCR. Phosphorylation of LAT tyrosine residues recruits multiple signaling proteins, leading to the assembly of the LAT signalosome, which is crucial for relaying signals that regulate T cell development and function. We previously showed that substitution of a negatively charged amino acid segment preceding the fifth tyrosine residue of LAT (Tyr127 in humans or Tyr132 in mouse LAT) enhances some early TCR signaling events, whereas downstream responses, such as Ca2+ influx and Erk phosphorylation, are partially inhibited. To investigate the physiological relevance of this segment in vivo, we generated a new LAT knock-in mouse strain (LatNIL) in which the negatively charged segment was replaced with a non-charged sequence. Unexpectedly, this mutation led to an alternative splicing event in the Lat gene that excluded exons 6 and 7, resulting in a frameshift, a premature stop codon at residue 145, and the loss of the six C-terminal tyrosine residues of LAT. Homozygous LatNIL/NIL mice showed a phenotype similar to that of LAT-knockout and Lat4YF mice (in which the four C-terminal tyrosines had been mutated to phenylalanine). Interestingly, homozygous LatNIL/NIL mice exhibited a distinct population of γδ T cells in lymphoid organs, which has not been observed in LAT-KO or Lat4YF mice. These γδ T cells expressed higher levels of CD27 compared to those in wild-type and LAT-KO mice, suggesting altered activation or differentiation states. Together, these data highlight how subtle alterations in LAT structure can profoundly impact T cell signaling and lineage composition
An Adaptive Nudging Scheme with Spatially Varying Gain for Improving the Ability of Ocean Temperature Assimilation in SPEEDY-NEMO
Get PDFNudging remains a cost-effective data assimilation technique in coupled climate models, yet conventional schemes with fixed spatial strengths struggle to represent heterogeneous ocean processes. This study introduces an adaptive nudging framework in which a spatially varying gain matrix dynamically balances model and observational errors, providing a more physically consistent determination of nudging coefficients. Implemented in the SPEEDY-NEMO coupled model, the method is systematically evaluated against a traditional latitude-dependent scheme. Results show substantial improvements in subsurface temperature assimilation across key regions, including the Niño3.4, tropical Indian Ocean, North Pacific, North Atlantic, and northeastern Pacific. The most pronounced gains occur above and within the thermocline, where strong stratification renders fixed nudging strengths inadequate, yielding a 20–30% reduction in RMSE and a 30–50% increase in correlation. In mid- to high-latitude regions, improvements extend to greater depths, consistent with deeper thermocline structures. The adaptive framework corrects both systematic bias and variance, enhancing not only the mean state but also variability representation. Additional benefits are found in salinity, currents, and sea surface height, demonstrating that spatially adaptive nudging provides a more effective and practical alternative for improving ocean state estimation in coupled models
Functional Characterization of Glucokinase Variants to Aid Clinical Interpretation of Monogenic Diabetes
Get PDFPrecision medicine starts with a precision diagnosis. Yet up to 80% of cases of monogenic diabetes, a form of diabetes characterized by mutations in a single gene, are either overlooked or misdiagnosed. A genetic test for monogenic diabetes does not always lead to a precise diagnosis, as novel variants are often classified as variants of unknown significance. Variant interpretation requires collation of a framework of evidence, including population, computational, and segregation data, and can be assisted by functional analysis. The inclusion of functional data can be challenging, depending on the number of benign and pathogenic variants available for benchmarking assays. Glucokinase is the rate-limiting step for glucose metabolism in the pancreatic beta-cell and governs the threshold for glucose-stimulated insulin release. Loss-of-function alleles in the glucokinase (GCK) gene are a cause of stable fasting hyperglycemia from birth and/or diabetes. In this study, we functionally characterized 25 variants identified during diagnostic testing or in exome sequencing studies. We assessed their kinetic characteristics, stability, and interaction with pharmacological and physiological regulators. We integrated our functional data with existing data from the ClinGen Monogenic Diabetes Variant Curation Expert Review panel using a gene-specific framework to assist variant classification. We show how functional evidence can aid variant classification, thus enabling diagnostic certainty
Complete genomes of Rickettsia typhi reveal a clonal population
Get PDFMurine typhus, caused by infection with Rickettsia typhi, is a neglected disease contributing to infectious disease burden in south- and southeast Asia. Despite its importance, we have minimal knowledge of the genomics of R. typhi, with only four complete genomes being sequenced prior to this work. We sequenced a further 25 genomes including historical strains collected before 1976 from both human and rat hosts, and recent genomes isolated from patients at a single hospital in Laos. Whole genome SNP analysis reveals extremely low levels of genetic diversity across the 29 genomes, with overall nucleotide diversity (π) of 1.27e-05 and evidence of purifying selection, and a minimal pan-genome. Phylogenetic analysis shows clustering of the genome by historic or modern origin, with the exception of one modern strain which is most closely related to historic strains from Thailand, and no clustering by host origin. The highly conserved genome of R. typhi suggests strong constraints on genome evolution in this obligate intracellular parasite, and has implications for the design of future murine typhus diagnostic tools and vaccines
Cosmological constraints from galaxy clustering and galaxy–galaxy lensing with extended SubHalo Abundance Matching
Get PDFWe present the first cosmological constraints from a joint analysis of galaxy clustering and galaxy–galaxy lensing using extended SubHalo Abundance Matching (SHAMe). We analyse stellar mass-selected Galaxy And Mass Assembly galaxy clustering and Kilo-Degree Survey (KiDS-1000) galaxy–galaxy lensing and find constraints on , in agreement with Planck at 1.7, with the mass density fluctuation amplitude in 8 sphere at present and the density parameter in total matter. These results are in agreement with the cosmic microwave background results from Planck. We are able to constrain all five SHAMe parameters, which describe the galaxy–subhalo connection. We validate our methodology by first applying it to simulated catalogues, generated from the TNG300 simulation, which mimic the stellar mass selection of our real data. We show that we are able to recover the input cosmology for both our fiducial and all-scale analyses. Our all-scale analysis extends to scales of galaxy–galaxy lensing below , which we exclude in our fiducial analysis to avoid baryonic effects. When including all scales, we find a value of , which is 1.26 higher than our fiducial result (against naive expectations where baryonic feedback should lead to small-scale power suppression), and in agreement with Planck at 0.9. We also find a 21 per cent tighter constraint on and a 29 per cent tighter constraint on compared to our fiducial analysis. This work shows the power and potential of joint small-scale galaxy clustering and galaxy–galaxy lensing analyses using SHAMe
Atypical presentation of high-grade non-Hodgkin lymphoma in a child: A diagnostic challenge
Get PDFThis case report describes an atypical presentation of high-grade Non-Hodgkin's Lymphoma (NHL) in a 10-year-old girl who presented to the emergency department with severe, unexplained flank pain and inability to walk, despite a lack of significant trauma history. Initial assessment revealed mild renal angle tenderness and a matted suprasternal lymph node, with laboratory results and preliminary imaging unremarkable. Persistent pain prompted advanced imaging, which identified a pathological spinal fracture and multiple masses consistent with aggressive NHL metastasis. Histopathological confirmation was achieved via lymph node biopsy. We highlight the diagnostic challenges posed by rare, atypical presentations of NHL in children, where symptoms may mimic benign conditions or minor trauma. Early suspicion and comprehensive diagnostic workup, including MRI and CT, were crucial for timely intervention. The patient was transferred to a pediatric oncology centre and achieved remission following chemotherapy. This report underscores the importance of maintaining a high index of suspicion for malignancy in children with unexplained pain or persistent symptoms, emphasizing the value of multidisciplinary collaboration and advanced imaging in early diagnosis