Conformational Analysis of 1,3-Difluorinated Alkanes.

Fluorine substitution can have a profound impact on molecular conformation. Here, we present a detailed conformational analysis of how the 1,3-difluoropropylene motif (-CHF-CH2-CHF-) determines the conformational profiles of 1,3-difluoropropane, anti- and syn-2,4-difluoropentane, and anti- and syn-3,5-difluoroheptane. It is shown that the 1,3-difluoropropylene motif strongly influences alkane chain conformation, with a significant dependence on the polarity of the medium. The conformational effect of 1,3-fluorination is magnified upon chain extension, which contrasts with vicinal difluorination. Experimental evidence was obtained from NMR analysis, where polynomial complexity scaling simulation algorithms were necessary to enable J-coupling extraction from the strong second-order spectra, particularly for the large 16-spin systems of the difluorinated heptanes. These results improve our understanding of the conformational control toolkit for aliphatic chains, yield simple rules for conformation population analysis, and demonstrate quantum mechanical time-domain NMR simulations for liquid state systems with large numbers of strongly coupled spins.

Vivarium: an interface and engine for integrative multiscale modeling in computational biology.

MOTIVATION: This article introduces Vivarium-software born of the idea that it should be as easy as possible for computational biologists to define any imaginable mechanistic model, combine it with existing models and execute them together as an integrated multiscale model. Integrative multiscale modeling confronts the complexity of biology by combining heterogeneous datasets and diverse modeling strategies into unified representations. These integrated models are then run to simulate how the hypothesized mechanisms operate as a whole. But building such models has been a labor-intensive process that requires many contributors, and they are still primarily developed on a case-by-case basis with each project starting anew. New software tools that streamline the integrative modeling effort and facilitate collaboration are therefore essential for future computational biologists. RESULTS: Vivarium is a software tool for building integrative multiscale models. It provides an interface that makes individual models into modules that can be wired together in large composite models, parallelized across multiple CPUs and run with Vivarium's discrete-event simulation engine. Vivarium's utility is demonstrated by building composite models that combine several modeling frameworks: agent-based models, ordinary differential equations, stochastic reaction systems, constraint-based models, solid-body physics and spatial diffusion. This demonstrates just the beginning of what is possible-Vivarium will be able to support future efforts that integrate many more types of models and at many more biological scales. AVAILABILITY AND IMPLEMENTATION: The specific models, simulation pipelines and notebooks developed for this article are all available at the vivarium-notebooks repository: https://github.com/vivarium-collective/vivarium-notebooks. Vivarium-core is available at https://github.com/vivarium-collective/vivarium-core, and has been released on Python Package Index. The Vivarium Collective (https://vivarium-collective.github.io) is a repository of freely available Vivarium processes and composites, including the processes used in Section 3. Supplementary Materials provide with an extensive methodology section, with several code listings that demonstrate the basic interfaces. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BioCRNpyler: Compiling chemical reaction networks from biomolecular parts in diverse contexts.

Biochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level design specification can be embedded into diverse biomolecular environments, such as cell-free extracts and in vivo milieus. Finally, our software toolbox has a parameter database, which allows users to rapidly prototype large models using very few parameters which can be customized later. By using BioCRNpyler, users ranging from expert modelers to novice script-writers can easily build, manage, and explore sophisticated biochemical models using diverse biochemical implementations, environments, and modeling assumptions.

Is unrestricted weight bearing immediately after fixation of rotationally unstable pelvic fractures safe?

INTRODUCTION: Rotationally unstable pelvic fractures treated with surgical fixation have traditionally been treated with restricted weight bearing on the affected side for 6-8 weeks post operatively. We have been developing pelvic fixation standards to allow for unrestricted weight bearing immediately post operatively in type B rotationally unstable pelvic fractures. AIMS: To assess for safety and efficacy of allowing unrestrictive weight bearing in this cohort of patients, we have clinically and radiologically monitored outcomes up to two years post operatively. METHODS: Through retrospective review, two cohorts of patients with Tile Type B pelvic fractures were identified that were treated at the Royal Adelaide Hospital, South Australia. Patient demographics, injury classification, surgical fixation and weight bearing status post operatively was recorded. One cohort of patients was allowed to fully weight bear post operatively, whilst the other was treated with 6 weeks of restricted post op weight bearing. At clinical follow up, post-operative x-rays were assessed for loss of reduction, screw or plate breakage and reoperation. RESULTS: Between January 2018 and January 2021, 53 patients with rotationally unstable pelvic fractures that underwent surgical fixation were included in this study. One group of patents were allowed to immediately weight bear as tolerated (WBAT) post operatively (n = 28) and the other with restricted weightbearing (RWB) (n = 25). There was 1 re operation for failure of fixation in each group. Metalwork breakage was more common in the WBAT group than in the RWB group and this was seen only in APC fractures. This increase in metalwork failure was not associated with loss of reduction. CONCLUSIONS: With surgical fixation, Tile type B rotationally unstable pelvic fractures can be allowed immediate weight bearing post operatively. We found this to be safe and effective, employing surgical strategies to address both anterior and posterior injuries to allow immediate unrestricted weight bearing. Broken metalwork was more commonly seen in the WBAT group but this was not associated with loss of reduction or reoperation.

A Cost Utility Analysis of Minimally Invasive Surgery with Thrombolysis Compared to Standard Medical Treatment in Spontaneous Intracerebral Haemorrhagic Stroke.

OBJECTIVES: Standard medical management of spontaneous intracerebral haemorrhage (ICH) and surgical hematoma evacuation starkly differ, and whilst landmark randomised control trials report no clinical benefit of early surgical evacuation compared with medical treatment in supratentorial ICH, minimally invasive surgery (MIS) with thrombolysis has been neglected within these studies. However, recent technological advancements in MIS have renewed interest in the surgical treatment of ICH. Several economic evaluations have focused on the benefits of MIS in ischaemic stroke management, but no economic evaluations have yet been performed comparing MIS to standard medical treatment for ICH. MATERIALS AND METHOD: All costs were sourced from the UK in GBP. Where possible, the 2019/2020 NHS reference costs were used. The MISTIE III study was used to analyse the outcomes of patients undergoing either MIS or standard medical treatment in this economic evaluation. RESULTS: The incremental cost-effectiveness ratio (ICER) for MIS was £485,240.26 for every quality-adjusted life year (QALY) gained. Although MIS resulted in a higher QALY compared to medical treatment, the gain was insignificant at 0.011 QALY. Four sensitivity analyses based on combinations of alternative EQ-5D values and categorisation of MIS outcomes, alongside alterations to the cost of significant adverse events, were performed to check the robustness of the ICER calculation. The most realistic sensitivity analysis showed a potential increase in cost effectiveness when clot size is reduced to <15ml, with the ICER falling to £74,335.57. DISCUSSION: From the perspective of the NHS, MIS with thrombolysis is not cost-effective compared to optimal medical treatment. ICER shows that intention-to-treat MIS would require a cost of £485,240.26 to gain one extra QALY, which is significantly above the NHS threshold of £30,000. Further UK studies with ICH survivor utilities, more replicable surgical technique, and the reporting of clot size reduction are indicated as the present sensitivity analysis suggests that MIS is promising. Greater detail about outcomes and complications would ensure improved cost-benefit analyses and support valid and efficient allocation of resources by the NHS.

Vibrational Spectroscopic Based Approach for Diagnosing Babesia bovis Infection.

Babesia bovis parasites present a serious and significant health concern for the beef and dairy industries in many parts of the world. Difficulties associated with the current diagnostic techniques include the following: they are prone to human error (microscopy) or expensive and time-consuming (polymerase chain reaction) to perform. Little is known about the biochemical changes in blood that are associated with Babesia infections. The discovery of new biomarkers will lead to improved diagnostic outcomes for the cattle industry. Vibrational spectroscopic technologies can record a chemical snapshot of the entire organism and the surrounding cell thereby providing a phenotype of the organism and the host infected cell. Here, we demonstrate the applicability of vibrational spectroscopic imaging techniques including Atomic Force Microscopy Infrared (AFM-IR) and confocal Raman microscopy to discover new biomarkers for B. bovis infections. Furthermore, we applied Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) to detect B. bovis in red blood cells (RBCs). Based on changes in the IR spectral bands, with ATR-FTIR in combination with Partial Least Squares-Discriminant Analysis we were able to discriminate infected samples from controls with a sensitivity and specificity of 92.0% and 91.7%, respectively, in less than 2 min, excluding sample extraction and preparation. The proposed method utilized a lysis approach to remove hemoglobin from the suspension of infected and uninfected cells, which significantly increased the sensitivity and specificity compared to measurements performed on intact infected red blood cells (intact infected RBC, 77.3% and 79.2%). This work represents a holistic spectroscopic study from the level of the single infected RBC using AFM-IR and confocal Raman to the detection of the parasite in a cell population using ATR-FTIR for a babesiosis diagnostic.

Evaluation of 4-Amino 2-Anilinoquinazolines against Plasmodium and Other Apicomplexan Parasites In Vitro and in a P. falciparum Humanized NOD-scid IL2Rγnull Mouse Model of Malaria.

A series of 4-amino 2-anilinoquinazolines optimized for activity against the most lethal malaria parasite of humans, Plasmodium falciparum, was evaluated for activity against other human Plasmodium parasites and related apicomplexans that infect humans and animals. Four of the most promising compounds from the 4-amino 2-anilinoquinazoline series were equally as effective against the asexual blood stages of the zoonotic P. knowlesi, suggesting that they could also be effective against the closely related P. vivax, another important human pathogen. The 2-anilinoquinazoline compounds were also potent against an array of P. falciparum parasites resistant to clinically available antimalarial compounds, although slightly less so than against the drug-sensitive 3D7 parasite line. The apicomplexan parasites Toxoplasma gondii, Babesia bovis, and Cryptosporidium parvum were less sensitive to the 2-anilinoquinazoline series with a 50% effective concentration generally in the low micromolar range, suggesting that the yet to be discovered target of these compounds is absent or highly divergent in non-Plasmodium parasites. The 2-anilinoquinazoline compounds act as rapidly as chloroquine in vitro and when tested in rodents displayed a half-life that contributed to the compound's capacity to clear P. falciparum blood stages in a humanized mouse model. At a dose of 50 mg/kg of body weight, adverse effects to the humanized mice were noted, and evaluation against a panel of experimental high-risk off targets indicated some potential off-target activity. Further optimization of the 2-anilinoquinazoline antimalarial class will concentrate on improving in vivo efficacy and addressing adverse risk.

Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression.

Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes. However, most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level. We have bridged these two methodologies with a multiscale mutation clustering algorithm that identifies variable length mutation clusters in cancer genes. We ran our algorithm on 539 genes using the combined mutation data in 23 cancer types from The Cancer Genome Atlas (TCGA) and identified 1295 mutation clusters. The resulting mutation clusters cover a wide range of scales and often overlap with many kinds of protein features including structured domains, phosphorylation sites, and known single nucleotide variants. We statistically associated these multiscale clusters with gene expression and drug response data to illuminate the functional and clinical consequences of mutations in our clusters. Interestingly, we find multiple clusters within individual genes that have differential functional associations: these include PTEN, FUBP1, and CDH1. This methodology has potential implications in identifying protein regions for drug targets, understanding the biological underpinnings of cancer, and personalizing cancer treatments. Toward this end, we have made the mutation clusters and the clustering algorithm available to the public. Clusters and pathway associations can be interactively browsed at m2c.systemsbiology.net. The multiscale mutation clustering algorithm is available at https://github.com/IlyaLab/M2C.

Seventeenth-Century 'double writing' schemes, and a 1676 letter in the phonetic script and real character of John Wilkins.

Royal Society Classified Papers XVI contains a letter written in not one but two seemingly mysterious scripts. As a result, this letter has remained until now effectively illegible, and has been miscatalogued. These scripts are rare examples of the written forms devised by John Wilkins to accompany his proposals for an artificial language, published under the auspices of the Royal Society in 1668. This article therefore first correctly identifies and decodes this letter, which is shown to be from the Somersetshire clergyman Andrew Paschall to Robert Hooke in London in 1676, and then surveys other surviving texts written in Wilkins's scripts or language. Finally the article addresses the contents of the letter, namely its author's attempt to build a workable double writing device, in effect an early 'pantograph'. Designs for such instruments had been much touted in the 1650s, and the complex history of such proposals is unravelled properly for the first time.

Combining dependent P-values with an empirical adaptation of Brown's method.

MOTIVATION: Combining P-values from multiple statistical tests is a common exercise in bioinformatics. However, this procedure is non-trivial for dependent P-values. Here, we discuss an empirical adaptation of Brown's method (an extension of Fisher's method) for combining dependent P-values which is appropriate for the large and correlated datasets found in high-throughput biology. RESULTS: We show that the Empirical Brown's method (EBM) outperforms Fisher's method as well as alternative approaches for combining dependent P-values using both noisy simulated data and gene expression data from The Cancer Genome Atlas. AVAILABILITY AND IMPLEMENTATION: The Empirical Brown's method is available in Python, R, and MATLAB and can be obtained from https://github.com/IlyaLab/CombiningDependentPvalues UsingEBM The R code is also available as a Bioconductor package from https://www.bioconductor.org/packages/devel/bioc/html/EmpiricalBrownsMethod.html CONTACT: Theo.Knijnenburg@systemsbiology.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Characterization of Integrase and Excisionase Activity in a Cell-Free Protein Expression System Using a Modeling and Analysis Pipeline.

We present a full-stack modeling, analysis, and parameter identification pipeline to guide the modeling and design of biological systems starting from specifications to circuit implementations and parametrizations. We demonstrate this pipeline by characterizing the integrase and excisionase activity in a cell-free protein expression system. We build on existing Python tools─BioCRNpyler, AutoReduce, and Bioscrape─to create this pipeline. For enzyme-mediated DNA recombination in a cell-free system, we create detailed chemical reaction network models from simple high-level descriptions of the biological circuits and their context using BioCRNpyler. We use Bioscrape to show that the output of the detailed model is sensitive to many parameters. However, parameter identification is infeasible for this high-dimensional model; hence, we use AutoReduce to automatically obtain reduced models that have fewer parameters. This results in a hierarchy of reduced models under different assumptions to finally arrive at a minimal ODE model for each circuit. Then, we run sensitivity analysis-guided Bayesian inference using Bioscrape for each circuit to identify the model parameters. This process allows us to quantify integrase and excisionase activity in cell extracts enabling complex-circuit designs that depend on accurate control over protein expression levels through DNA recombination. The automated pipeline presented in this paper opens up a new approach to complex circuit design, modeling, reduction, and parametrization.

Identifying and understanding the factors that influence the functioning of integrated healthcare systems in the NHS: a systematic literature review.

OBJECTIVES: The National Health Service has been moving towards integrated care for the best part of two decades to address the growing financial and service pressures created by an ageing population. Integrated healthcare systems (IHSs) join up health and social care services and have been established to manage the care of individuals with complex chronic conditions but with varied success. It is therefore imperative to conduct a Systematic Literature Review (SLR) to identify and understand the factors that influence their successful functioning, and ascertain the factor with the greatest influence, in order to ensure positive outcomes when establishing future IHSs. METHODS: Articles published between 1 January 1997 and 8 March 2020 were analysed from the following six databases: Healthcare Management Information Consortium, Nuffield Trust, Cumulative Index to Nursing and Allied Health Literature, PubMed, National Institute for Health and Care Excellence Evidence and Health Systems Evidence. Those deemed relevant after title and abstract screening were procured for subsequent review of the full-text article. RESULTS: Thirty-three finalised articles were analysed in this SLR to provide a comprehensive overview of the factors that influence the functioning of IHSs. Factors were stratified into six key categories: organisational culture, workforce management, interorganisational collaboration, leadership ability of staff, economic factors and political factors. Leadership was deemed to be the most influential factor due to its intrinsic and instrumental role in influencing the other key factors. CONCLUSIONS: The findings of this SLR may serve as a guide to developing tailor-made recommendations and policies that address the identified key factors and thereby improve the functioning of present and future IHSs. Furthermore, due to both its overarching influence and the inadequacy of literature in this field, there is a strong case for further research exploring leadership development specifically for IHSs.

The Accuracy of Percutaneous Sacro-Iliac Screw Fixation for Pelvic Ring Injuries using the Lateral view as the Corner Stone for Screw Placement: A Prospective Cohort Study.

This paper has been temporarily removed by the publisher, Wolters-Kluwer, as it may have been published in error. We regret any confusion this may have caused.

Telehealth in cancer care during the COVID-19 pandemic.

INTRODUCTION: The Victorian COVID-19 Cancer Network (VCCN) Telehealth Expert Working Group aimed to evaluate the telehealth (TH) experience for cancer patients, carers and clinicians with the rapid uptake of TH in early 2020 during the COVID-19 pandemic. METHODS: We conducted a prospective multi-centre cross-sectional survey involving eight Victorian regional and metropolitan cancer services and three consumer advocacy groups. Patients or their carers and clinicians who had TH consultations between 1 July 2020 and 31 December 2020 were invited to participate in patient and clinician surveys, respectively. These surveys were opened from September to December 2020. RESULTS: The acceptability of TH via both video (82.9%) and phone (70.4%) were high though acceptability appeared to decrease in older phone TH users. Video was associated with higher satisfaction compared to phone (87.1% vs 79.7%) even though phone was more commonly used. Various themes from the qualitative surveys highlighted barriers and enablers to rapid TH implementation. DISCUSSION: The high TH acceptability supports this as a safe and effective strategy for continued care and should persist beyond the pandemic environment, where patient preferences are considered and clinically appropriate. Ongoing support to health services for infrastructure and resources, as well as expansion of reimbursement eligibility criteria for patients and health professionals, including allied health and nursing, are crucial for sustainability.

Interprosthetic femoral fractures managed with modern distal femoral locking plates: 10 years' experience at a UK major trauma centre.

INTRODUCTION: Interprosthetic femoral fractures (IFF) are rare but increasing with an ageing population. Operative management is challenging and there is currently a paucity of outcome data in literature. The purpose of this study was to evaluate outcomes of IFFs managed with modern distal femoral locking plates, in a larger sample size than previously published. METHOD: This retrospective study reviewed 49 closed IFFs in 48 patients at a major trauma center from 2009 to 2019 occurring between previous total hip arthroplasty (n=38), hemi hip arthroplasty (n=3), dynamic hip screw (n=6) or cephalomedullary nail (n=2) and total knee arthroplasty. They were managed with Minimally Invasive Plate Osteosynthesis (MIPO) employing modern biological fixation techniques and stabilised with VA-LCP Condylar (Synthes; n=28) or Peri-Loc (S&N; n=21) plate. Clinical and radiographic outcomes were measured. RESULTS: The majority of fractures were in female patients (80%), who were elderly (average 83 years), and comorbid (55% ASA grade 3 or 4). Most fractures were Pires type IIA and OTA/AO type 33A. Average plate spanning femur was 16 holes, with average working length of 6 holes. 86% had unrestricted weight bearing immediately post operatively. 31 fractures reached radiological (n=25) or clinical (n=6) union. 13 patients died with 2 lost to follow up. There were 3 non-unions, with implant failure occurring before 4 months in all 3. We present a union rate of 91% (n=31/34). CONCLUSION: IFFs are occurring with increasing frequency in a frail elderly population. In patients with IFFs, MIPO and biological fixation techniques using modern distal femoral locking plates can achieve high rate of union when combined with immediate unrestricted weight bearing postoperatively.

Short or long intramedullary devices for hip fracture? A systematic review of the evidence.

Trochanteric hip fractures may be fixed with either sliding hip screws or intramedullary devices. Current UK guidance is that intramedullary fixation should be used for AO/OTA 31A3 fractures but does not stipulate length of nail. We present a systematic review comparing short and long nails for these injuries in older patients. Three studies were randomized, all with methodological concerns. None demonstrated a clinically significant difference in outcome. There is no good evidence to support long over short intramedullary devices in this scenario. Evidence is required to demonstrate whether the potentially increased surgical risk confers any benefits in this group.

Theodoricus Gravius (fl. 1600-1661): some biographical notes on a German chymist and scribe working in seventeenth-century England.

This article establishes the career of Theodoricus Gravius (fl. 1600-1661), a German refugee who worked in Great Linford as a laboratory assistant and scribe to the cleric and practitioner of astrological medicine, Richard Napier (1559-1634). Gravius was the first transmitter to England of the texts of the mystic Jacob Böhme, and although he settled in England, he undertook subsequent foreign visits to attempt the recovery of his property and to learn more about chymical matters. He also visited the Oxonian George Hakewill (1578-1649), and is responsible for scribing one of the manuscripts of the revisions to Hakewill's celebrated Apologie or Declaration Concerning the Power and Providence of God (1635).

Babesiosis Vaccines: Lessons Learned, Challenges Ahead, and Future Glimpses.

The incidence and prevalence of babesiosis in animals and humans is increasing, yet prevention, control, or treatment measures remain limited and ineffective. Despite a growing body of new knowledge of the biology, pathogenicity, and virulence of Babesia parasites, there is still no well-defined, adequately effective and easily deployable vaccine. While numerous published studies suggest that the development of such anti-Babesia vaccines should be feasible, many others identify significant challenges that need to be overcome in order to succeed. Here, we review historic and recent attempts in babesiosis vaccine discovery to avoid past pitfalls, learn new lessons, and provide a roadmap to guide the development of next-generation babesiosis vaccines.

Unravelling the cellular and molecular pathogenesis of bovine babesiosis: is the sky the limit?

The global impact of bovine babesiosis caused by the tick-borne apicomplexan parasites Babesia bovis, Babesia bigemina and Babesia divergens is vastly underappreciated. These parasites invade and multiply asexually in bovine red blood cells (RBCs), undergo sexual reproduction in their tick vectors (Rhipicephalus spp. for B. bovis and B. bigemina, and Ixodes ricinus for B. divergens) and have a trans-ovarial mode of transmission. Babesia parasites can cause acute and persistent infections to adult naïve cattle that can occur without evident clinical signs, but infections caused by B. bovis are associated with more severe disease and increased mortality, and are considered to be the most virulent agent of bovine babesiosis. In addition, babesiosis caused by B. divergens has an important zoonotic potential. The disease caused by B. bovis and B. bigemina can be controlled, at least in part, using therapeutic agents or vaccines comprising live-attenuated parasites, but these methods are limited in terms of their safety, ease of deployability and long-term efficacy, and improved control measures are urgently needed. In addition, expansion of tick habitats due to climate change and other rapidly changing environmental factors complicate efficient control of these parasites. While the ability to cause persistent infections facilitates transmission and persistence of the parasite in endemic regions, it also highlights their capacity to evade the host immune responses. Currently, the mechanisms of immune responses used by infected bovines to survive acute and chronic infections remain poorly understood, warranting further research. Similarly, molecular details on the processes leading to sexual reproduction and the development of tick-stage parasites are lacking, and such tick-specific molecules can be targets for control using alternative transmission blocking vaccines. In this review, we identify and examine key phases in the life-cycle of Babesia parasites, including dependence on a tick vector for transmission, sexual reproduction of the parasite in the midgut of the tick, parasite-dependent invasion and egression of bovine RBCs, the role of the spleen in the clearance of infected RBCs (IRBCs), and age-related disease resistance in cattle, as opportunities for developing improved control measures. The availability of integrated novel research approaches including "omics" (such as genomics, transcriptomics, and proteomics), gene modification, cytoadhesion assays, RBC invasion assays and methods for in vitro induction of sexual-stage parasites will accelerate our understanding of parasite vulnerabilities. Further, producing new knowledge on these vulnerabilities, as well as taking full advantage of existing knowledge, by filling important research gaps should result in the development of next-generation vaccines to control acute disease and parasite transmission. Creative and effective use of current and future technical and computational resources are needed, in the face of the numerous challenges imposed by these highly evolved parasites, for improving the control of this disease. Overall, bovine babesiosis is recognised as a global disease that imposes a serious burden on livestock production and human livelihood, but it largely remains a poorly controlled disease in many areas of the world. Recently, important progress has been made in our understanding of the basic biology and host-parasite interactions of Babesia parasites, yet a good deal of basic and translational research is still needed to achieve effective control of this important disease and to improve animal and human health.

Delay to surgery does not affect survival following osteoporotic femoral fractures.

AIMS: Fragility femoral fractures occur in a similar group of patients to hip fractures but they are not routinely managed along standardised guidelines. This study looked specifically at whether delay to surgery has an impact on mortality and morbidity. PATIENTS AND METHODS: An international, multi-centre retrospective review was carried including all patients over 60 years with fragility femoral fractures, including most periprosthetic fractures, between December 2008-2014. RESULTS: 243 patients met the inclusion criteria with mean follow-up 25 months. 197 (81%) were female with mean age 81 years. Median time to surgery was 2 days; 39% were operated on <24h, 23% 24-48h, and 37% at >48h. 3- and 12-month mortality were 14% (95% CI: 9-18%) and 26% (20-31%) respectively. On Kaplan-Meier plotting, relationships were apparent between survival and sex, and ASA grade, but not delay to surgery or fracture type. CONCLUSION: Fragility femoral fractures have equivalent mortality to hip fractures but we found no link between delay to surgery and mortality. We believe it is safe to delay surgery, within reason, whilst their acute and chronic medical problems are optimised. We believe this information will help develop guidelines similar to hip fracture pathways.