Developing a serocorrelate of protection against invasive group B streptococcus disease in pregnant women: a feasibility study.

BACKGROUND: Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure. OBJECTIVES: The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design. DESIGN: Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018). SETTING: Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales. PARTICIPANTS: Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus. RESULTS: A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V). LIMITATIONS: Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants. CONCLUSIONS: We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study. FUTURE WORK: A large case-control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information

Method for separating single-wall carbon nanotubes and compositions thereof

The invention relates to a process for sorting and separating a mixture of (n, m) type single-wall carbon nanotubes according to (n, m) type. A mixture of (n, m) type single-wall carbon nanotubes is suspended such that the single-wall carbon nanotubes are individually dispersed. The nanotube suspension can be done in a surfactant-water solution and the surfactant surrounding the nanotubes keeps the nanotube isolated and from aggregating with other nanotubes. The nanotube suspension is acidified to protonate a fraction of the nanotubes. An electric field is applied and the protonated nanotubes migrate in the electric fields at different rates dependent on their (n, m) type. Fractions of nanotubes are collected at different fractionation times. The process of protonation, applying an electric field, and fractionation is repeated at increasingly higher pH to separated the (n, m) nanotube mixture into individual (n, m) nanotube fractions. The separation enables new electronic devices requiring selected (n, m) nanotube types

Preferred orientation in fibers of HiPco single wall carbon nanotubes from diffuse x-ray scattering

Neat Fibers of HiPco single wall carbon nanotubes extruded from strong acid suspensions exhibit preferred orientation along fiber axes. We characterize the extrusion-induced alignment using x-ray fiber diagrams and polarized Raman scattering, using a model which allows for some fraction of the sample to remain completely unaligned. We show that both x-ray and Raman data are required for a complete texture analysis of SWNT fibers

Thermoelectric Power of p-Doped Single-Wall Carbon Nanotubes and the Role of Phonon Drag

We measured thermoelectric power S of bulk single-wall carbon nanotube (SWNT) materials p-doped with acids. In contrast to oxygen-exposed or degassed samples, S is very small at the lowest temperatures, increases super-linearly above a characteristic and sample-dependent T, and then levels off. We attribute this unusual behavior to 1-D phonon drag, in which the depression of the Fermi energy cuts off electron-phonon scattering at temperatures below a characteristic T0. This idea is supported by a model calculation in which the low temperature behavior of phonon drag is specifically related to the one-dimensional character of the electronic spectrum

Single Wall Carbon Nanotube Fibers Extruded from Super-Acid Suspensions: Preferred Orientation, Electrical and Thermal Transport

Fibers of single wall carbon nanotubes extruded from super-acid suspensions exhibit preferred orientation along their axes. We characterize the alignment by x-ray fiber diagrams and polarized Raman scattering, using a model which allows for a completely unaligned fraction. This fraction ranges from 0.17 to 0.05±0.02 for three fibers extruded under different conditions, with corresponding Gaussian full widths at half-maximum (FWHM) from 64o to 44o±2o. FWHM, aligned fraction, electrical and thermal transport all improve with decreasing extrusion orifice diameter. Resistivity, thermoelectric power and resonant-enhanced Raman scattering indicate that the neat fibers are strongly p-doped; the lowest observed ρ is 0.25mΩcm at 300 K. High temperature annealing increases ρ by more than 1 order of magnitude and restores the Raman resonance associated with low-energy van Hove transitions, without affecting the nanotube alignment

Macroscopic Neat Single-Walled Carbon Nanotubes Fibers

The first-ever well-aligned continuous macroscopic neat single-walled carbon nanotube (SWNT) fibers were produced using conventional spinning techniques. Neat SWNT fibers, containing no surfactant or polymer, were made by spinning dispersions of SWNTs in 102% sulfuric acid into different coagulants. The critical role of sulfuric acid in dispersing and aligning SWNTs during fiber formation has been explored. Characterization shows alignment greater than any other macroscopic neat SWNT material reported to-date while providing insight into the fundamental hierarchy and nature of SWNT fiber formation. Electrical, thermal, and mechanical measurements indicate that neat SWNT fibers hold tremendous potential for future applications

Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation

Objectives: Hepatic CEACAM1 expression declines with advanced hepatic fibrosis stage in patients with metabolic dysfunction-associated steatohepatitis (MASH). Global and hepatocyte-specific deletions of Ceacam1 impair insulin clearance to cause hepatic insulin resistance and steatosis. They also cause hepatic inflammation and fibrosis, a condition characterized by excessive collagen production from activated hepatic stellate cells (HSCs). Given the positive effect of PPARg on CEACAM1 transcription and on HSCs quiescence, the current studies investigated whether CEACAM1 loss from HSCs causes their activation. Methods: We examined whether lentiviral shRNA-mediated CEACAM1 donwregulation (KD-LX2) activates cultured human LX2 stellate cells. We also generated LratCre þ Cc1fl/fl mutants with conditional Ceacam1 deletion in HSCs and characterized their MASH phenotype. Media transfer experiments were employed to examine whether media from mutant human and murine HSCs activate their wild-type counterparts. Results: LratCre þ Cc1fl/fl mutants displayed hepatic inflammation and fibrosis but without insulin resistance or hepatic steatosis. Their HSCs, like KD-LX2 cells, underwent myofibroblastic transformation and their media activated wild-type HSCs. This was inhibited by nicotinic acid treatment which blunted the release of IL-6 and fatty acids, both of which activate the epidermal growth factor receptor (EGFR) tyrosine kinase. Gefitinib inhibition of EGFR and its downstream NF-kB/IL-6/STAT3 inflammatory and MAPK-proliferation pathways also blunted HSCs activation in the absence of CEACAM1. Conclusions: Loss of CEACAM1 in HSCs provoked their myofibroblastic transformation in the absence of insulin resistance and hepatic steatosis. This response is mediated by autocrine HSCs activation of the EGFR pathway that amplifies inflammation and proliferation

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Introduction Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age

Humanity's Last Exam

Benchmarks are important tools for tracking the rapid advancements in large language model (LLM) capabilities. However, benchmarks are not keeping pace in difficulty: LLMs now achieve over 90\% accuracy on popular benchmarks like MMLU, limiting informed measurement of state-of-the-art LLM capabilities. In response, we introduce Humanity's Last Exam (HLE), a multi-modal benchmark at the frontier of human knowledge, designed to be the final closed-ended academic benchmark of its kind with broad subject coverage. HLE consists of 3,000 questions across dozens of subjects, including mathematics, humanities, and the natural sciences. HLE is developed globally by subject-matter experts and consists of multiple-choice and short-answer questions suitable for automated grading. Each question has a known solution that is unambiguous and easily verifiable, but cannot be quickly answered via internet retrieval. State-of-the-art LLMs demonstrate low accuracy and calibration on HLE, highlighting a significant gap between current LLM capabilities and the expert human frontier on closed-ended academic questions. To inform research and policymaking upon a clear understanding of model capabilities, we publicly release HLE at https://lastexam.ai