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The Greenland shark (Somniosus microcephalus) is a large species of shark found in the North Atlantic and Arctic Oceans and is believed to be the longest living vertebrate. Relatively little is known about its biology, abundance, health or diseases. In March 2022, only the third reported UK stranding of this species occurred and it was the first to undergo post-mortem examination. The animal was a sexually immature female, measuring 3.96 m in length and 285 kg in weight, and was in poor nutritional state. Gross findings included haemorrhages in the skin and soft tissues, particularly of the head, and silt in the stomach suggestive of live stranding, bilateral corneal opacity, slightly turbid cerebrospinal fluid (CSF) and patchy congestion of the brain. Histopathological findings included keratitis and anterior uveitis, fibrinonecrotic and lymphohistiocytic meningitis of the brain and proximal spinal cord and fibrinonecrotizing choroid plexitis. A near pure growth of a Vibrio organism was isolated from CSF. This is believed to be the first report of meningitis in this species. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in multidisciplinary management, patients with biliary tract cancer have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. To our knowledge, no studies have described a benefit of adjuvant therapy. We aimed to determine whether adjuvant capecitabine improved overall survival compared with observation following surgery for biliary tract cancer.Methods: This randomised, controlled, multicentre, phase 3 study was done across 44 specialist hepatopancreatobiliary centres in the UK. Eligible patients were aged 18 years or older and had histologically confirmed cholangiocarcinoma or muscle-invasive gallbladder cancer who had undergone a macroscopically complete resection (which includes liver resection, pancreatic resection, or, less commonly, both) with curative intent, and an Eastern Cooperative Oncology Group performance status of less than 2. Patients who had not completely recovered from previous surgery or who had previous chemotherapy or radiotherapy for biliary tract cancer were also excluded. Patients were randomly assigned 1:1 to receive oral capecitabine (1250 mg/m2 twice daily on days 1-14 of a 21-day cycle, for eight cycles) or observation commencing within 16 weeks of surgery. Treatment was not masked, and allocation concealment was achieved with a computerised minimisation algorithm that stratified patients by surgical centre, site of disease, resection status, and performance status. The primary outcome was overall survival. As prespecified, analyses were done by intention to treat and per protocol. This study is registered with EudraCT, number 2005-003318-13.Findings: Between March 15, 2006, and Dec 4, 2014, 447 patients were enrolled; 223 patients with biliary tract cancer resected with curative intent were randomly assigned to the capecitabine group and 224 to the observation group. The data cutoff for this analysis was March 6, 2017. The median follow-up for all patients was 60 months (IQR 37-60). In the intention-to-treat analysis, median overall survival was 51·1 months (95% CI 34·6-59·1) in the capecitabine group compared with 36·4 months (29·7-44·5) in the observation group (adjusted hazard ratio [HR] 0·81, 95% CI 0·63-1·04; p=0·097). In a protocol-specified sensitivity analysis, adjusting for minimisation factors and nodal status, grade, and gender, the overall survival HR was 0·71 (95% CI 0·55-0·92; p=0·010). In the prespecified per-protocol analysis (210 patients in the capecitabine group and 220 in the observation group), median overall survival was 53 months (95% CI 40 to not reached) in the capecitabine group and 36 months (30-44) in the observation group (adjusted HR 0·75, 95% CI 0·58-0·97; p=0·028). In the intention-to-treat analysis, median recurrence-free survival was 24·4 months (95% CI 18·6-35·9) in the capecitabine group and 17·5 months (12·0-23·8) in the observation group. In the per-protocol analysis, median recurrence-free survival was 25·9 months (95% CI 19·8-46·3) in the capecitabine group and 17·4 months (12·0-23·7) in the observation group. Adverse events were measured in the capecitabine group only, and of the 213 patients who received at least one cycle, 94 (44%) had at least one grade 3 toxicity, the most frequent of which were hand-foot syndrome in 43 (20%) patients, diarrhoea in 16 (8%) patients, and fatigue in 16 (8%) patients. One (<1%) patient had grade 4 cardiac ischaemia or infarction. Serious adverse events were observed in 47 (21%) of 223 patients in the capecitabine group and 22 (10%) of 224 patients in the observation group. No deaths were deemed to be treatment related.Interpretation: Although this study did not meet its primary endpoint of improving overall survival in the intention-to-treat population, the prespecified sensitivity and per-protocol analyses suggest that capecitabine can improve overall survival in patients with resected biliary tract cancer when used as adjuvant chemotherapy following surgery and could be considered as standard of care. Furthermore, the safety profile is manageable, supporting the use of capecitabine in this setting.Funding: Cancer Research UK and Roche. [ABSTRACT FROM AUTHOR]

Biomedical catheters are commonly used to move fluids from one part of the body to another, or remove them from the body completely. In some instances, these catheters become occluded due to blood or other debris. Such occlusions may prove fatal or require re-operation with enormous costs and effects on the health-care system and the individual. We developed a model of occlusion in both a ventriculo-peritoneal shut system and en external ventricular drain. Having demonstrated that occlusions can be reliably generated in a manner that resembles the clinical situation we show that vibration can clear the blockages. Vibration in the 50–60 Hz range was able to maintain patency in the catheters or to clear the blockage when the catheter was completely occluded. In high concentrations of blood, 150 s of vibration applied every 30 min was able to maintain the patency of the catheter. Clinically, as the level of blood in the fluid decreases, the time intervals between vibration applications could be increased. We believe that vibration offers a safe, non-invasive method to maintain the patency of biomedical catheters. [ABSTRACT FROM AUTHOR]

Abstract: Choristoderes are a group of extinct diapsid reptiles that once occupied the freshwater systems in the Northern Hemisphere from the Middle Jurassic through the Miocene. The Early Cretaceous monjurosuchid Philydrosaurus from western Liaoning, China, represents a transitional morphotype between a broad-snouted (crocodile-like) and a narrow-snouted (gavial-like) skull during the evolution of Choristodera. New specimens of the taxon from the Early Cretaceous Jiufotang Formation include an incomplete braincase and a nearly complete juvenile skeleton; the study of these specimens provides new information on the braincase and ontogenetic change of the skeleton of this transitional monjurosuchid. In the braincase floor, the foramen internus canalis caroticus externus opens in a groove lateral to the constricted lateral aspect of the parasphenoid, and ventral exposure of this foramen differs from Champsosaurus, in which parasphenoid/pterygoid fusion completely encloses the canal. On the occiput, the vagus nerve foramen penetrates the basioccipital, while the two foramina for the hypoglossal nerve open at the exoccipital/basioccipital suture. Comparative study of the new juvenile specimen with adult Philydrosaurus reveals previously unknown developmental changes of the cranial and postcranial skeleton of this monjurosuchid. Ontogenetically, Philydrosaurus underwent a dramatic change of skull proportions, including elongation of the antorbital and postorbital regions, and elongation of the jaws, with a great increase of the number of marginal teeth. The lower temporal fenestra is entirely closed in early ontogeny, as in large, fully-grown adults. [Copyright &y& Elsevier]

Recent attention has been paid to the inadequacy of using the ratio V max/K M as a measure of enzyme performance, particularly in the context of industrial biocatalysis. This can lead to misleading expectations of enzyme performance and can be troublesome when used to select among different variants for scale-up evaluation under process conditions. To address these issues, we derive the average velocity based on the time-integrated behavior of the enzyme over the course of the reaction. The resulting expression, deemed catalytic effectiveness, captures important features of the system that have heretofore been ignored (such as highly variable substrate and/or product concentrations and inhibition) and offers a rigorous way to compare enzymes for their capacity to carry out industrial transformations. [Copyright &y& Elsevier]

Directed evolution is a powerful tool for the creation of commercially useful enzymes, particularly those approaches that are based on in vitro recombination methods, such as DNA shuffling. Although these types of search algorithms are extraordinarily efficient compared with purely random methods, they do not explicitly represent or interrogate the genotype–phenotype relationship and are essentially blind in nature. Recently, however, researchers have begun to apply multivariate statistical techniques to model protein sequence–function relationships and guide the evolutionary process by rapidly identifying beneficial diversity for recombination. In conjunction with state-of-the-art library generation methods, the statistical approach to sequence optimization is now being used routinely to create enzymes efficiently for industrial applications. [Copyright &y& Elsevier]

Abstract: An incomplete lower jaw with teeth documents the presence of a new genus and species of placental mammal from the Upper Cretaceous (Lancian; late Maastrichtian) Frenchman Formation, Saskatchewan, Canada. This new mammal is characterized by highly compressed lower molars that decrease in size from m1 to m3 and superficially resemble the molars of Tertiary Mesonychia. These resemblances, however, are interpreted as convergent, and the new mammal is classified in its own family and incertae sedis at the ordinal level. This new mammal thus joins other recent discoveries in western Canada of mammals of Tertiary aspect (Condylarthra; Taeniodonta) occurring in the Late Cretaceous. [Copyright &y& Elsevier]

Examines whether corporate travel managers' criticisms of frequent-flier programs vary with company size. Survey of corporate travel manager members of the National Business Travel Association; Perceived waste caused by frequent-flier programs; Universally held opinions concerning frequent-flier programs.

• Functional Data Analysis provides tools for studying multi-species indices. • A huge simplification in terms of dimensional reduction is achieved. • Comparisons are made with percentage trends which crudely represent complex changes. • Differences in species patterns of occupancy and abundance are found. • Recommendations for accompanying visualisations for biodiversity indicators are made. Multi-species indicators are widely used to condense large, complex amounts of information on multiple separate species by forming a single index to inform research, policy and management. Much detail is typically lost when such indices are constructed. Here we investigate the potential of Functional Data Analysis, focussing upon Functional Principal Component Analysis (FPCA), which can be easily carried out using standard R programs, as a tool for displaying features of the underlying information. Illustrations are provided using data from the UK Butterflies for the New Millennium and UK Butterfly Monitoring Scheme databases. The FPCAs conducted result in a huge simplification in terms of dimensional reduction, allowing species occupancy and abundance to be reduced to two and three dimensions, respectively. We show that a functional principal component arises for both occupancy and abundance analyses that distinguishes between species that increase or decrease over time, and that it differs from percentage trend, which is a simplification of complex temporal changes. We find differences in species patterns of occupancy and abundance, providing a warning against routinely combining both types of index within multi-species indicators, for example when using occupancy as a proxy for abundance when insufficient abundance data are available. By identifying the differences between species, figures displaying functional principal component scores are much more informative than the simple bar plots of percentages of significant trends that often accompany multi-species indicators. Informed by the outcomes of the FPCA, we make recommendations for accompanying visualisations for multi-species indicators, and discuss how these are likely to be context and audience specific. We show that, in the absence of FPCA, using mean species occupancy and total abundance can provide additional, accessible information to complement species-level trends. At the simplest level, we suggest using jitter plots to display variation in species-level trends. We encourage further application to other taxa, and recommend the routine augmentation of multi-species indicators in the future with additional statistical procedures and figures, to serve as an aid to improve communication and understanding of biodiversity metrics, as well as reveal potentially hidden patterns of behaviour and guide additional directions for investigation. [ABSTRACT FROM AUTHOR]

Abstract: An effective, asymmetric total synthesis of the antibiotic (+)-sorangicin A (1) has been achieved. Central to this venture was the development of first- and second-generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a Co2(CO)6–alkyne complex, the second involving a KHMDS-promoted epoxide ring formation/opening cascade. Additional highlights include effective construction of the dihydro- and tetrahydropyran ring systems, respectively, via a stereoselective conjugate addition/α-oxygenation protocol and a thioketalization/hydrostannane reduction sequence. Late-stage achievements entailed two Julia–Kociénski olefinations to unite three advanced fragments with high E-stereoselectivity, followed by a modified Stille protocol to introduce the Z,Z,E trienoate moiety, thereby completing the carbon skeleton. Mukaiyama macrolactonization, followed by carefully orchestrated Lewis and protic acid-promoted deprotections that suppressed isomerization and/or destruction of the sensitive (Z,Z,E)-trienoate linkage completed the first, and to date only, total synthesis of (+)-sorangicin A (1). [Copyright &y& Elsevier]

Abstract: Spinal epidural hematoma is a rare clinical entity and has a varied etiology. Urgent surgical evacuation to prevent serious permanent neurologic deficits is generally indicated. We describe a case of a 52-year-old man, on oral anticoagulant therapy, who presented with Brown-Sequard syndrome due to spontaneous spinal epidural hematoma at the cervicothoracic junction. This diagnosis was initially overlooked, given the asymmetric pattern of deficit. He later underwent cervical laminectomy and had complete restoration of neurologic function. [Copyright &y& Elsevier]

Abstract: A fundamental problem in estimating biodiversity loss is that very little quantitative data are available for insects, which comprise more than two-thirds of terrestrial species. We present national population trends for a species-rich and ecologically diverse insect group: widespread and common macro-moths in Britain. Two-thirds of the 337 species studied have declined over the 35yr study and 21% (71) of the species declined >30% 10yr−1. If IUCN (World Conservation Union) criteria are applied at the national scale, these 71 species would be regarded as threatened. The declines are at least as great as those recently reported for British butterflies and exceed those of British birds and vascular plants. These results have important and worrying implications for species such as insectivorous birds and bats, and suggests as-yet undetected declines may be widespread among temperate-zone insects. [Copyright &y& Elsevier]

: ObjectiveTo investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium.: DesignClinical, placebo-controlled, randomized trial study.: SettingHealthy volunteers in an academic research environment.: Patient(s)Fifty-five dancers (mean age: 22.0 ± 4.6, age at menarche: 14.7 ± 2.3 years), including 24 amenorrheics.: Intervention(s)Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day.: Main outcome measure(s)Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine.: Result(s)Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization.: Conclusion(s)These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea. [Copyright &y& Elsevier]

• Opportunistic citizen science is valuable for biodiversity trend analysis. • Participants in citizen science vary in their recording behaviour. • Estimated trends in occupancy were robust to differences in recorder behaviour. • Species occupancy itself was more sensitive to some aspects of recorder behaviour. Opportunistic species sightings submitted by citizen science volunteers are a valuable source of species data for trends analysis, as used in biodiversity indicators. However, projects collecting these data give people flexibility where and when to make records, and the recording behaviour of participants varies between individuals. Here we tested the effect of recorder behaviour on outputs of the analysis of temporal biodiversity trends. Using a large (c. 3 million records), 20 year unstructured citizen science dataset of butterfly records in Great Britain, we manipulated recorder behaviour by constructing biased 50% subsamples of the dataset by preferentially including different types of recorders (based on high and low values of four metrics independently describing the temporal, spatial and taxonomic attributes of recorder behaviour). We found that, in general, the three outputs (namely: occupancy trend, precision of the trend, and the estimate of occupancy) showed relatively little deviation from random expectation across most of the different types of recorder behaviour. Occupancy trends showed least deviation, while estimates of occupancy itself showed greatest deviation from the random expectation. Regarding the recorder behaviours, the outputs were most sensitive to variation in 'recorder potential', which describes the difference between 'thorough' and 'incidental' recorders. Importantly, by demonstrating the robustness of occupancy trends to differences in recorder behaviour, this study provides support for the appropriate use of occupancy trend modelling for unstructured citizen science. However, we did not consider change in recorder behaviour over time, so further research is required to assess the impact of this on trend modelling. This study highlights the value of developing solutions to further increase the robustness of biodiversity trend analysis. These solutions should include both analytical developments and enhancements in project design to engage participants. [ABSTRACT FROM AUTHOR]

It is important for conservationists to be able to assess the risks that climate change poses to species, in order to inform decision making. Using standardised and repeatable methods, we present a national-scale assessment of the risks of range loss and opportunities for range expansion that climate change could pose for over 3000 plants and animals. Species were selected by their occurrence in England, the primary focus of the study, but climate change impacts were assessed across Great Britain, widening their geographical relevance. A basic risk assessment that compared projected future changes in potential range with recently observed changes classified 21% of species as being at high risk and 6% at medium risk of range loss under a B1 climate change scenario. A greater number of species were classified as having a medium (16%) or high (38%) opportunity to potentially expand their distribution. A more comprehensive assessment, incorporating additional ecological information, including potentially confounding and exacerbating factors (e.g. dispersal, habitat availability and other constraints), was applied to 402 species, of which 35% were at risk of range loss and 42% may expand their range extent. This study covers a temperate region with a significant proportion of species at their poleward range limit; the balance of risks and opportunities from climate change may be different elsewhere. The outcome of both risk assessments varied between taxonomic groups, with bryophytes and vascular plants containing the greatest proportion of species at risk from climate change. Upland habitats contained more species at risk than other habitats. Whilst the overall pattern was clear, confidence was generally low for individual assessments, with the exception of well-studied taxa such as birds. In response to climate change, nature conservation needs to plan for changing species distributions and an uncertain future. [ABSTRACT FROM AUTHOR]

Background Optimal surgical management for flexion-distraction cervical spine injuries remains controversial with current guidelines recommending anterior, posterior, and circumferential approaches. Here, we determined the incidence of and examined risk factors for clinical and radiographic failure in patients with 1-segment cervical distraction injuries having undergone anterior surgical fixation. Methods A retrospective review of 57 consecutive patients undergoing anterior fixation for subaxial flexion-distraction cervical injuries between 2008 and 2012 at our institution was performed. The primary outcome was the number of patients requiring additional surgical stabilization and/or radiographic failure. Data collected included age, gender, mechanism and level of injury, facet pattern injury, and vertebral end plate fracture. Results A total of 6 patients failed clinically and/or radiographically (11%). Four patients (7%) required additional posterior fixation. Although 2 other patients identified met radiographic failure criteria, at follow-up they had fused radiographically, were stable clinically, and no further treatment was pursued. Progressive kyphosis and translation were found to be significantly correlated with need for revision ( P < 0.05 and P = 0.02, respectively). No differences were identified for all other clinical and radiologic factors assessed, including unilateral or bilateral facet injury, facet fracture, and end plate fracture. Conclusion This study contributes to the growing body of evidence supporting anterior fixation alone for flexion-distraction injuries. Findings suggest that current measurements of radiographic failure including segmental translation and kyphosis may predict radiographic failure and need for further surgical stabilization in some patients. Future follow-up studies assessing for independent risk factors for anterior approach failure with a validated predictive scoring model should be considered. [ABSTRACT FROM AUTHOR]

Invasive alien species, including pests and diseases of plants and animals, are a major cause of biodiversity change and may impact upon human well-being and the economy. If new, potentially invasive, taxa arrive then it is most cost-effective to respond as early in their establishment as possible. Information to support this can be gained from volunteers, i.e. via citizen science. However, it is vital to develop ways of quantifying volunteer recorder effort to assess its contribution to the detection of rare events, such as the arrival of invasive alien species. We considered the potential to detect adult oak processionary moths ( Thaumetopoea processionea ) by amateur naturalists recording moths at light traps. We calculated detection rates from the Netherlands, where T. processionea is widely established and poses a risk to tree health and human health, and applied these to the spatial pattern of moth recording effort in the UK. The probability of recording T. processionea in the Netherlands varied across provinces from 0.05–2.4% per species of macro-moth recorded on a list of species (so equalling 1–52% for a list of 30 species). Applying these rates to the pattern of moth recording in the UK: T. processionea could be detected (detection > 0%), if it were present, in 69% and 4.7% of 10 km and 1 km squares, respectively. However, in most squares detection probability is low (< 1% of 1 km squares have annual detection probability of > 10%). Our study provides a means to objectively assess the use of citizen science as a monitoring tool in the detection of rare events, e.g. the arrival of invasive alien species, occurrence of rare species and natural colonisation. [ABSTRACT FROM AUTHOR]

Purpose: To report the outcome of oral chlorambucil as a single treatment in patients with orbital mucosa-associated lymphoid tissue (MALT) lymphoma. Design: Retrospective nonrandomized clinical study. Participants: Thirty-three patients with isolated orbital MALT lymphoma. Methods: Medical records of all patients with histology-verified orbital MALT lymphoma treated with oral chlorambucil at the Royal Melbourne Hospital were reviewed. Main Outcome Measures: Complete clinical response, partial response, local relapse, systemic extension (distant relapse), and survival. Results: Thirty-three patients (19 female; mean age, 69 years) participated in the study. Patients received an average of 4 courses of oral chlorambucil with a mean total dose of 600 mg. The lacrimal gland was the most frequent site of occurrence (24%), followed by the conjunctiva, eyelid, and superior orbit. Orbital mass, swelling, and diplopia were common presenting signs. Complete response was noted in 26 patients (79%). In 2 of the patients with complete clinical response, mild residual thickening was noted on follow-up orbital imaging studies. Four patients (12%) showed disease recurrence or relapse. Mean follow-up time was 32 (±20) months (range, 8 months–6 years; median, 26 months). None of the patients developed granulocytopenia secondary to chemotherapy, and none suffered significant nausea or vomiting. One patient with malignant transformation died 12 months after diagnosis and initial treatment. Conclusions: Systemic chemotherapy with chlorambucil is a reasonable option in patients with orbital MALT lymphoma. It is associated with minimal to no side effects. Additionally, it may be well tolerated by elderly patients and also may treat subclinical disease elsewhere. [Copyright &y& Elsevier]

The mechanisms that regulate the transition between the initial priming phase and DNA replication in liver regeneration are poorly understood. To study this transition, we compared events occurring after standard two-thirds partial hepatectomy, which elicits full regeneration, with response to a reduced hepatectomy, onethird partial hepatectomy (⅓PH), which leads to little DNA replication. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between the two procedures, cell cycle progression was significantly blunted in ⅓PH mice. Among the main defects observed in ⅓PH mice were an almost complete deficiency in retinoblastoma phosphorylation and the lack of increase in kinase activity associated with cyclin E. We report that, in two-thirds partial hepatectomy mice, the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) preceded the start of DNA replication and was not detectable in ⅓PH animals. Injection of HB-EGF into ⅓PH mice resulted in a > 15-fold increase in DNA replication. Moreover, we show that hepatocyte DNA replication was delayed in HB-EGF knock-out mice. In summary, we show that HB-EGF is a key factor for hepatocyte progression through G1/S transition during liver regeneration. [ABSTRACT FROM AUTHOR]