Resistance to genetic insect control: modelling the effects of space

Genetic insect control, such as self-limiting RIDL(2) (Release of Insects Carrying a Dominant Lethal) technology, is a development of the sterile insect technique which is proposed to suppress wild populations of a number of major agricultural and public health insect pests. This is achieved by mass rearing and releasing male insects that are homozygous for a repressible dominant lethal genetic construct, which causes death in progeny when inherited. The released genetically engineered ('GE') insects compete for mates with wild individuals, resulting in population suppression. A previous study modelled the evolution of a hypothetical resistance to the lethal construct using a frequency-dependent population genetic and population dynamic approach. This found that proliferation of resistance is possible but can be diluted by the introgression of susceptible alleles from the released homozygous-susceptible GE males. We develop this approach within a spatial context by modelling the spread of a lethal construct and resistance trait, and the effect on population control, in a two deme metapopulation, with GE release in one deme. Results show that spatial effects can drive an increased or decreased evolution of resistance in both the target and non-target demes, depending on the effectiveness and associated costs of the resistant trait, and on the rate of dispersal. A recurrent theme is the potential for the non-target deme to act as a source of resistant or susceptible alleles for the target deme through dispersal. This can in turn have a major impact on the effectiveness of insect population control

FORAMINIFERAL CHARACTERISATION OF MID-UPPER JURASSIC SEQUENCES IN THE WESSEX BASIN (UNITED KINGDOM)

The use of foraminifera in the characterisation of sequences (systems tracts, maximum flooding surfaces, etc.) has developed over the last decade. Much of this work has been based in the Cenozoic successions of the Gulf of Mexico, although there is a growing application of such data in the Middle East and the North Sea Basin. The easiest surface to characterise has been the maximum flooding surface with its high diversity and high(er) abundance faunas; the characterisation of individual systems tracts has been less successful. Using the well-known mid-Upper Jurassic successions of the Dorset coastal sections, we have investigated a number of high resolution (para)sequences for their foraminiferal content. Using data of foraminiferal diversity and standing crops from a range of modern substrates we have investigated the potential faunas available after deposition, taphonomy, compaction, groundwater dissolution and modern weathering. By understanding the processes involved we have identified the key foraminiferal features of typical mid-Upper Jurassic sequences and indicated how this work may help in the correlation of successions in North Dorset and Normandy

Food provision for older people receiving home care from the perspectives of home-care workers

Malnutrition is a significant cause of morbidity and mortality, particularly among older people. Attention has focused on the inadequacies of food provision in institutions, yet the majority suffering from malnutrition live in the community. The aim of this study was to explore barriers and facilitators to food provision for older people receiving home care. It was a qualitative exploratory study using semi-structured interviews with nine home-care workers in June 2013 employed by independent agencies in a large city in northern England. Data were analysed thematically, based on the principles of grounded theory. Findings showed that significant time pressures limited home-care workers in their ability to socially engage with service users at mealtimes, or provide them with anything other than ready meals. Enabling choice was considered more important than providing a healthy diet, but choice was limited by food availability and reliance on families for shopping. Despite their knowledge of service users and their central role in providing food, home-care workers received little nutritional training and were not involved by healthcare professionals in the management of malnutrition. Despite the rhetoric of individual choice and importance of social engagement and nutrition for health and well-being, nutritional care has been significantly compromised by cuts to social care budgets. The potential role for home-care workers in promoting good nutrition in older people is undervalued and undermined by the lack of recognition, training and time dedicated to food-related care. This has led to a situation whereby good quality food and enjoyable mealtimes are denied to many older people on the basis that they are unaffordable luxuries rather than an integral component of fundamental care. © 2014 John Wiley & Sons Ltd

Massive pulmonary embolism in patients with extreme bleeding risk: a case series on the successful use of ultrasound-assisted, catheter directed thrombolysis in a district general hospital

This is the final version. Available from the publisher via the DOI in this record.Massive pulmonary embolism (PE), characterised by profound arterial hypotension, is a life-threatening emergency with a 90-day mortality of over 50%. Systemic thrombolysis can signifcantly reduce the risk of death or cardiovascular collapse in these patients, by around 50%, but these benefts are ofset by a fvefold increased risk of intracranial haemorrhage and major bleeding, which may limit its use in patients at high risk of catastrophic haemorrhage. We describe a case series of 3 patients presenting with massive PE, each with extreme risk of bleeding and contra-indication to systemic thrombolysis, treated successfully with ultrasound-assisted, catheter directed thrombolysis (U-ACDT). Our experience of this novel technique using the EkoSonic Endovascular System (Ekos, BTG, London, UK) on carefully selected patients has demonstrated the potential to improve clinical status in shocked patients, with minimal bleed risk. There have been several clinical studies evaluating the Ekos system. Both the ULTIMA and SEATTLE II studies have shown signifcant reductions in RV/LV ratio by CT scanning when compared to standard anticoagulation in patients with intermediate-risk PE, with minimal bleeding complications. However, there is a pressing need for a randomised trial demonstrating improvement in robust clinical outcomes when comparing U-ACDT to simple anticoagulation. We believe that this case series adds new insight and highlights the potential of catheter directed thrombolysis in this high-risk patient cohort and consideration should be made to its use in cases where systemic thrombolysis is felt to be too high ris

Predicting in-hospital mortality and unanticipated admissions to the intensive care unit using routinely collected blood tests and vital signs: development and validation of a multivariable model.

AIM: The National Early Warning System (NEWS) is based on vital signs; the Laboratory Decision Tree Early Warning Score (LDT-EWS) on laboratory test results. We aimed to develop and validate a new EWS (the LDTEWS:NEWS risk index) by combining the two and evaluating the discrimination of the primary outcome of unanticipated intensive care unit (ICU) admission or in-hospital mortality, within 24 hours. METHODS: We studied emergency medical admissions, aged 16 years or over, admitted to Oxford University Hospitals (OUH) and Portsmouth Hospitals (PH). Each admission had vital signs and laboratory tests measured within their hospital stay. We combined LDT-EWS and NEWS values using a linear time-decay weighting function imposed on the most recent blood tests. The LDTEWS:NEWS risk index was developed using data from 5 years of admissions to PH, and validated on a year of data from both PH and OUH. We tested the risk index's ability to discriminate the primary outcome using the c-statistic. RESULTS: The development cohort contained 97,933 admissions (median age = 73 years) of which 4,723 (4.8%) resulted in in-hospital death and 1,078 (1.1%) in unanticipated ICU admission. We validated the risk index using data from PH (n = 21,028) and OUH (n = 16,383). The risk index showed a higher discrimination in the validation sets (c-statistic value (95% CI)) (PH, 0.901 (0.898-0.905); OUH, 0.916 (0.911-0.921)), than NEWS alone (PH, 0.877 (0.873-0.882); OUH, 0.898 (0.893-0.904)). CONCLUSIONS: The LDTEWS:NEWS risk index increases the ability to identify patients at risk of deterioration, compared to NEWS alone

Peptide Cross-Linked Poly(2-oxazoline) as a Sensor Material for the Detection of Proteases with a Quartz Crystal Microbalance

Inflammatory conditions are frequently accompanied by increased levels of active proteases, and there is rising interest in methods for their detection to monitor inflammation in a point of care setting. In this work, new sensor materials for disposable single-step protease biosensors based on poly(2-oxazoline) hydrogels cross-linked with a protease-specific cleavable peptide are described. The performance of the sensor material was assessed targeting the detection of matrix metalloproteinase-9 (MMP-9), a protease that has been shown to be an indicator of inflammation in multiple sclerosis and other inflammatory conditions. Films of the hydrogel were formed on gold-coated quartz crystals using thiol–ene click chemistry, and the cross-link density was optimized. The degradation rate of the hydrogel was monitored using a quartz crystal microbalance (QCM) and showed a strong dependence on the MMP-9 concentration. A concentration range of 0–160 nM of MMP-9 was investigated, and a lower limit of detection of 10 nM MMP-9 was determined

A comparison of the ability of the National Early Warning Score and the National Early Warning Score 2 to identify patients at risk of in-hospital mortality: A multi-centre database study.

AIMS: To compare the ability of the National Early Warning Score (NEWS) and the National Early Warning Score 2 (NEWS2) to identify patients at risk of in-hospital mortality and other adverse outcomes. METHODS: We undertook a multi-centre retrospective observational study at five acute hospitals from two UK NHS Trusts. Data were obtained from completed adult admissions who were not fit enough to be discharged alive on the day of admission. Diagnostic coding and oxygen prescriptions were used to identify patients with type II respiratory failure (T2RF). The primary outcome was in-hospital mortality within 24 h of a vital signs observation. Secondary outcomes included unanticipated intensive care unit admission or cardiac arrest within 24 h of a vital signs observation. Discrimination was assessed using the c-statistic. RESULTS: Among 251,266 adult admissions, 48,898 were identified to be at risk of T2RF by diagnostic coding. In this group, NEWS2 showed statistically significant lower discrimination (c-statistic, 95% CI) for identifying in-hospital mortality within 24 h (0.860, 0.857-0.864) than NEWS (0.881, 0.878-0.884). For 1394 admissions with documented T2RF, discrimination was similar for both systems: NEWS2 (0.841, 0.827-0.855), NEWS (0.862, 0.848-0.875). For all secondary endpoints, NEWS2 showed no improvements in discrimination. CONCLUSIONS: NEWS2 modifications to NEWS do not improve discrimination of adverse outcomes in patients with documented T2RF and decrease discrimination in patients at risk of T2RF. Further evaluation of the relationship between SpO2 values, oxygen therapy and risk should be investigated further before wide-scale adoption of NEWS2

Photoelectrochemical imaging system for the mapping of cell surface charges

The surface charge of cells affects cell signaling, cell metabolic processes, adherence to surfaces, and cell proliferation. Our understanding of the role of membrane charges is limited due to the inability to observe changes without interfering, chemically or physically, with the cell or its membrane. Here, we report that a photoelectrochemical imaging system (PEIS) based on label-free ac-photocurrent measurements at indium tin oxide (ITO) coated glass substrates can be used to map the basal surface charge of single live cells under physiological conditions. Cells were cultured on the ITO substrate. Photocurrent images were generated by scanning a focused, modulated laser beam across the back of the ITO coated glass substrate under an applied bias voltage. The photocurrent was shown to be sensitive to the negative surface charge of the substrate facing, basal side of a single living cell—an area not accessible to other electrochemical or electrophysiological imaging techniques. The PEIS was used to monitor the lysis of mesenchymal stem cells