Protocol for a prospective cohort study of open tibia fractures in Malawi with a nested implementation of open fracture guidelines.

Background: Road traffic injury (RTI) is the largest cause of death amongst 15-39-year-old people worldwide, and the burden of injuries such as open tibia fractures are rapidly increasing in Malawi. This study aims to investigate disability and economic outcomes of people with open tibia fractures in Malawi and improve these with locally delivered implementation of open fracture guidelines. Methods: This is a prospective cohort study describing function, quality of life and economic burden of open tibia fractures in Malawi. In total, 160 participants will be recruited across six centres and will be followed-up with face-to-face interviews at six weeks, three months, six months and one year following injury. The primary outcome will be function at one year measured by the short musculoskeletal functional assessment (SMFA) score. Secondary outcomes will include quality of life measured by EuroQol EQ-5D-3L, catastrophic loss of income and implementation outcomes (acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability) at one year. A nested pilot pre-post implementation study of an interventional bundle for all open fractures will be developed based on other implementation studies from low- and middle-income countries (LMICs). Regression analysis will be used to model and investigate associations between SMFA score and fracture severity, infection and the pre- and post-training course period. Outcome: This prospective cohort study will report patient reported outcomes from open tibia fractures in low-resource settings. Subsequent detailed evaluation of both the clinical and implementation components of the study will promote sustainability of improved open fractures management in the study sites and further scale-up of open fracture management guidelines. Ethics: Ethics approval has been obtained from the Liverpool School of Tropical Medicine and College of Medicine Research and Ethics committee

On the Continuous Formation of Field Spheroidal Galaxies in Hierarchical Models of Structure Formation

We re-examine the assembly history of field spheroidals as a potentially powerful discriminant of galaxy formation models. Whereas monolithic collapse and hierarchical, merger-driven, models suggest radically different histories for these galaxies, neither the theoretical predictions nor the observational data for field galaxies have been sufficiently reliable for precise conclusions to be drawn. A major difficulty in interpreting the observations, reviewed here, concerns the taxonomic definition of spheroidals in merger-based models. Using quantitative measures of recent star formation activity drawn from the internal properties of a sample of distant field galaxies in the Hubble Deep Fields, we undertake a new analysis to assess the continuous formation of spheroidal galaxies. Whereas abundances and redshift distributions of modelled spheroidals are fairly insensitive to their formation path, we demonstrate that the distribution and amount of blue light arising from recent mergers provides a more sensitive approach. With the limited resolved data currently available, the rate of mass assembly implied by the observed colour inhomogeneities is compared to that expected in popular Lambda-dominated cold dark matter models of structure formation. These models produce as many highly inhomogeneous spheroidals as observed, but underpredict the proportion of homogeneous, passive objects. We conclude that colour inhomogeneities, particularly when combined with spectroscopic diagnostics for large, representative samples of field spheroidals, will be a more valuable test of their physical assembly history than basic source counts and redshift distributions. Securing such data should be a high priority for the Advanced Camera for Surveys on Hubble Space Telescope.Comment: 14 pages, 7 figures, submitted to MNRA

Analysis of Immune Checkpoint Drug Targets and Tumor Proteotypes in Non-Small Cell Lung Cancer

New therapeutics targeting immune checkpoint proteins have significantly advanced treatment of non-small cell lung cancer (NSCLC), but protein level quantitation of drug targets presents a critical problem. We used multiplexed, targeted mass spectrometry (MS) to quantify immunotherapy target proteins PD-1, PD-L1, PD-L2, IDO1, LAG3, TIM3, ICOSLG, VISTA, GITR, and CD40 in formalin-fixed, paraffin-embedded (FFPE) NSCLC specimens. Immunohistochemistry (IHC) and MS measurements for PD-L1 were weakly correlated, but IHC did not distinguish protein abundance differences detected by MS. PD-L2 abundance exceeded PD-L1 in over half the specimens and the drug target proteins all displayed different abundance patterns. mRNA correlated with protein abundance only for PD-1, PD-L1, and IDO1 and tumor mutation burden did not predict abundance of any protein targets. Global proteome analyses identified distinct proteotypes associated with high PD-L1-expressing and high IDO1-expressing NSCLC. MS quantification of multiple drug targets and tissue proteotypes can improve clinical evaluation of immunotherapies for NSCLC

The Origin of the Hubble Sequence in Lambda-CDM Cosmology

The Galform semi-analytic model of galaxy formation is used to explore the mechanisms primarily responsible for the three types of galaxies seen in the local universe: bulge, bulge+disk and disk, identified with the visual morphological types E, S0/a-Sbc, and Sc-Scd, respectively. With a suitable choice of parameters the Galform model can accurately reproduce the observed local K_s-band luminosity function (LF) for galaxies split by visual morphological type. The successful set of model parameters is used to populate the Millennium Simulation with 9.4 million galaxies and their dark matter halos. The resulting catalogue is then used to explore the evolution of galaxies through cosmic history. The model predictions concur with recent observational results including the galaxy merger rate, the star formation rate and the seemingly anti-hierarchical evolution of ellipticals. However, the model also predicts significant evolution of the elliptical galaxy LF that is not observed. The discrepancy raises the possibility that samples of z~1 galaxies which have been selected using colour and morphological criteria may be contaminated with galaxies that are not actually ellipticals.Comment: Accepted for publication in MNRAS. Missing reference adde

Overcoming the barriers to implementing urban road user charging schemes

Urban road user charging offers the potential to achieve significant improvements in urban transport, but is notoriously difficult to implement. Cities need guidance on the range of factors to be considered in planning and implementing such schemes. This paper summarises the results of a 3 year programme which has collated evidence on the issues of most concern to cities. A state of the art report has provided evidence on 14 themes, ranging from objectives and design to implementation and evaluation. A set of 16 case studies has reviewed experience in design and implementation across Europe. The paper summarises their findings, provides references to more detailed information, presents the resulting policy recommendations to European, national and local government, and outlines the areas in which further research is needed

Improving the management of open tibia fractures, Malawi.

To assess the impact of an open fracture intervention bundle on clinical management and patient outcomes of adults in Malawi with open tibia fractures. We conducted a before-and-after implementation study in Malawi in 2021 and 2022 to assess the impact of an open fracture intervention bundle, including a national education course for clinical officers and management guidelines for open fractures. We recruited 287 patients with open tibia fractures. The primary outcome was a before-and-after comparison of the self-reported short musculoskeletal function assessment score, a measure of patient function. Secondary outcomes included clinical management; and clinician knowledge and implementation evaluation outcomes of 57 health-care providers attending the course. We also constructed multilevel regression models to investigate associations between clinical knowledge, patient function, and implementation evaluation before and after the intervention. The median patient function score at 1 year was 6.8 (interquartile range, IQR: 1.5 to 14.5) before intervention and 8.4 (IQR: 3.8 to 23.2) after intervention. Compared with baseline scores, we found clinicians' open fracture knowledge scores improved 1 year after the intervention was implemented (mean posterior difference: 1.6, 95% highest density interval: 0.9 to 2.4). However, we found no difference in most aspects of clinicians' open fracture management practice. Despite possible improvement in clinician knowledge and positive evaluation of the intervention implementation, our study showed that there was no overall improvement in clinical management, and weak evidence of worsening patient function 1 year after injury, after implementation of the open fracture intervention bundle

Stoichiometry and the New Biology: The Future Is Now

There is a call for biological science to move away from the reductionist focus of the past, but there are large-scale integrative efforts already underway; biological stoichiometry provides one such example