The Clover Root Weevil Invasion: Impact and Response of the New Zealand Pastoral Industry 1996-2012

Clover root weevil, Sitona lepidus Gyllenhall (Curculionidae: Coleoptera), was first reported in New Zealand in 1996. With few natural enemies or competitors, it rapidly became a major pest of white clover. Its strong flight capability, tendency to be transported in agricultural machinery and vehicles, and wide climatic tolerance enabled it to spread the length of the country (1,600 km) by 2010. The most damaging stage is the larva, which attacks the roots, root nodules and stolons of clovers, reducing herbage production (particularly in spring), pasture clover content, and nitrogen fixation. From the time of the initial invasion, the pastoral industry supported research into management as insecticides were not a viable option. Nitrogen fertiliser applications after grazing were recommended to maintain production. Field evaluations showed that white clovers with good general agronomic adaptation survived better under weevil pressure than less-adapted clovers. In 2006, a parasitic wasp, Microctonus aethiopoides Loan (Braconidae: Hymenoptera), was introduced from Ireland for biological control of S. lepidus. It has also established and dispersed very rapidly, and often suppresses weevil populations within 2 – 3 years of its establishment in a new locality. Involvement of industry field consultants was an essential aspect of the biological control release programme in the North Island where the weevil was already widespread before M. aethiopoides was introduced

Transforming encounters: A review of the drivers and mechanisms of macrofaunal plastic fragmentation in the environment

Plastic has infiltrated every ecosystem on the planet, making encounters between this anthropogenic pollutant and fauna inevitable. Abiotic environmental breakdown involving light, oxygen, temperature and mechanical forces is well-characterized, while biotic degradation mechanisms are less well-understood. Reports of the role of macrofauna in the fragmentation of plastic debris are increasing. This review explores the driving factors for macrofaunal fragmentation, as well as the physiological mechanisms by which plastic items are fragmented. The presence, and access to plastic within an organism’s habitat are the key determinants of macrofaunal plastic degradation. Foraging strategies, along with burrowing and nesting behaviors increase the likelihood of macrofauna interacting with plastics. Though this type of fragmentation can occur externally, it often follows ingestion, which in itself can be driven by resemblance to food. Four physical mechanisms of macrofaunal plastic fragmentation were identified, namely biting, drilling, grazing and grinding. Biting, restricted to the mouthparts of an organism, was the most common form of macrofaunal fragmentation reported in literature. Similarly, the use of specialized mouthparts for drilling or grazing can produce secondary plastic particles. Lastly, grinding, through manipulation by the gizzard or gastric mill following ingestion can significantly reduce the size of the plastic material. Prolonged and/or repeated interactions with plastics pose the risk of increased wear on the mouthparts and digestive organs involved. Through mechanisms that directly affect the plastic’s structural integrity, physical fragmentation by macrofauna can amplify overall plastic degradation rates and the formation of micro- and nanoplastics in the environment, while long internal retention times can contribute to their dispersal, trophic transfer, and the organism’s exposure to plastic additives. To more fully understand the extent of macrofaunal plastic fragmentation and allow predictive modeling, we suggest the reporting of evidence in a unified and systematic way. Our findings further highlight the urgency for the implementation of a global plastic waste management system to reduce the burden of micro- and nanoplastics

A group intervention to improve quality of life for people with advanced dementia living in care homes: the Namaste feasibility cluster RCT

Background People with advanced dementia who live and die in nursing homes experience variable quality of life, care and dying. There is a need to identify appropriate, cost-effective interventions that facilitate high-quality end-of-life care provision. Objectives To establish the feasibility and acceptability to staff and family of conducting a cluster randomised controlled trial of the Namaste Care intervention for people with advanced dementia in nursing homes. Design The study had three phases: (1) realist review and (2) intervention refinement to inform the design of (3) a feasibility cluster randomised controlled trial with a process evaluation and economic analysis. Clusters (nursing homes) were randomised in a 3 : 1 ratio to intervention or control (usual care). The nature of the intervention meant that blinding was not possible. Setting Nursing homes in England providing care for people with dementia. Participants Residents with advanced dementia (assessed as having a Functional Assessment Staging Test score of 6 or 7), their informal carers and nursing home staff. Intervention Namaste Care is a complex group intervention that provides structured personalised care in a dedicated space, focusing on enhancements to the physical environment, comfort management and sensory engagement. Main outcome measures The two contender primary outcome measures were Comfort Assessment in Dying – End of Life Care in Dementia for quality of dying (dementia) and Quality of Life in Late Stage Dementia for quality of life. The secondary outcomes were as follows: person with dementia, sleep/activity (actigraphy), neuropsychiatric symptoms, agitation and pain; informal carers, satisfaction with care at the end of life; staff members, person-centred care assessment, satisfaction with care at the end of life and readiness for change; and other data – health economic outcomes, medication/service use and intervention activity. Results Phase 1 (realist review; 86 papers) identified that a key intervention component was the activities enabling the development of moments of connection. In phase 2, refinement of the intervention enabled the production of a user-friendly 16-page A4 booklet. In phase 3, eight nursing homes were recruited. Two homes withdrew before the intervention commenced; four intervention and two control homes completed the study. Residents with advanced dementia (n = 32) were recruited in intervention (n = 18) and control (n = 14) homes. Informal carers (total, n = 12: intervention, n = 5; control, n = 7) and 97 staff from eight sites (intervention, n = 75; control, n = 22) were recruited over a 6-month period. Recruitment is feasible. Completion rates of the primary outcome questionnaires were high at baseline (100%) and at 4 weeks (96.8%). The Quality of Life in Late Stage Dementia was more responsive to change over 24 weeks. Even where economic data were missing, these could be collected in a full trial. The intervention was acceptable; the dose varied depending on the staffing and physical environment of each care home. Staff and informal carers reported changes for the person with dementia in two ways: increased social engagement and greater calm. No adverse events related to the intervention were reported. Conclusions A subsequent definitive trial is feasible if there are amendments to the recruitment process, outcome measure choice and intervention specification. Future work In a full trial, consideration is needed of the appropriate outcome measure that is sensitive to different participant responses, and of clear implementation principles for this person-centred intervention in a nursing home context. Trial registration Current Controlled Trials ISRCTN14948133. 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. 24, No. 6. See the NIHR Journals Library website for further project information

Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator

A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible “wait anaphase” signal to the vicinity of the spindle

Outcome of COVID-19 in hospitalised immunocompromised patients:An analysis of the WHO ISARIC CCP-UK prospective cohort study

Background: Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic. Methods and findings: We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. Approximately 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent. Conclusions: Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group. Trial registration: ISRCTN 66726260

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.

Background: This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. Funding: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation

Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study.

OBJECTIVE: To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). DESIGN: Prospective observational cohort study with rapid data gathering and near real time analysis. SETTING: 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). PARTICIPANTS: 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. MAIN OUTCOME MEASURES: Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. RESULTS: Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 109/L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group. CONCLUSIONS: Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). STUDY REGISTRATION: ISRCTN66726260

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study

BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). FINDINGS: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. INTERPRETATION: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

What is the recovery rate and risk of long-term consequences following a diagnosis of COVID-19?:A harmonised, global longitudinal observational study protocol

Introduction: Very little is known about possible clinical sequelae that may persist after resolution of acute COVID-19. A recent longitudinal cohort from Italy including 143 patients followed up after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60-day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical intensive care unit patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. The primary aim of this study is to characterise physical and psychosocial sequelae in patients post-COVID-19 hospital discharge. Methods and analysis: This is an international open-access prospective, observational multisite study. This protocol is linked with the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) and the WHO’s Clinical Characterisation Protocol, which includes patients with suspected or confirmed COVID-19 during hospitalisation. This protocol will follow-up a subset of patients with confirmed COVID-19 using standardised surveys to measure longer term physical and psychosocial sequelae. The data will be linked with the acute phase data. Statistical analyses will be undertaken to characterise groups most likely to be affected by sequelae of COVID-19. The open-access follow-up survey can be used as a data collection tool by other follow-up studies, to facilitate data harmonisation and to identify subsets of patients for further in-depth follow-up. The outcomes of this study will inform strategies to prevent long-term consequences; inform clinical management, interventional studies, rehabilitation and public health management to reduce overall morbidity; and improve long-term outcomes of COVID-19. Ethics and dissemination: The protocol and survey are open access to enable low-resourced sites to join the study to facilitate global standardised, longitudinal data collection. Ethical approval has been given by sites in Colombia, Ghana, Italy, Norway, Russia, the UK and South Africa. New sites are welcome to join this collaborative study at any time. Sites interested in adopting the protocol as it is or in an adapted version are responsible for ensuring that local sponsorship and ethical approvals in place as appropriate. The tools are available on the ISARIC website (www.isaric.org)