Patients' practices and experiences of using nebuliser therapy in the management of COPD at home.

How patients use their nebulisers at home is vital to ensure effective treatment and optimal health outcomes for patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to identify the practicalities and problems associated with nebuliser use by patients with COPD at home, which may impact on the safety and effectiveness of therapy

Retest reliability of measuring hip extensor muscle strength in different testing positions in young people with cerebral palsy

Abstract Background In young people with spastic diplegic cerebral palsy weakness of the hip extensor muscles are associated with limitations in activity. It is important that clinicians can reliably measure hip extensor muscle strength to monitor changes over time and the effects of any interventions. Previous research has demonstrated high reliability for measuring strength of all muscles of the lower limb, with the exception of the hip extensors. Therefore the aim of this study was to examine the retest reliability of measuring hip extensor strength in young people with cerebral palsy. Methods Using a test-retest reliability research design, 19 participants with spastic diplegic cerebral palsy (Gross Motor Function Classification System Levels II and III) (mean 19 y 2 mo [S D 2 y 5 mo]) attended two testing sessions held 12 weeks apart. Three trials with a hand-held dynamometer were taken at each testing session in supine, prone and standing. Retest reliability was calculated with Intraclass Correlation Coefficients (ICC(2,1)) and with units of measurement (kilograms) converted to a percentage strength change. Results ICC values ranged from .74 to .78 in supine, .75 to .80 in prone, and .73 to .75 in standing. To be 95% confident that real change had occurred, an individual's strength would need to increase 55 to 60% in supine, 86 to 102% in prone, and 102 to 105% in standing. To be 95% confident that real change had occurred across groups, strength would need to increase 4 to 8% in supine, 22 to 31% in prone, and 32% to 34% in standing. Higher ICC values were observed when three trials were used for testing. Conclusions The supine testing position was more reliable than the prone or standing testing positions. It is possible to measure hip extensor strength with sufficient reliability to be able monitor change within groups using the supine position provided three trials are used during testing. However, there is insufficient reliability to monitor changes in hip extensor strength in individuals with cerebral palsy unless they exhibit very large strength increases.</p

Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that markers can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response

The influence of submesoscales and vertical mixing on the export of sinking tracers in large-eddy simulations

AbstractWe use idealized large-eddy simulations (LES) and a simple analytical theory to study the influence of submesoscales on the concentration and export of sinking particles from the mixed layer. We find that restratification of the mixed layer following the development of submesoscales reduces the rate of vertical mixing which, in turn, enhances the export rate associated with gravitational settling. For a neutral tracer initially confined to the mixed layer, subinertial (submesoscale) motions enhance the downward tracer flux, consistent with previous studies. However, the sign of the advective flux associated with the concentration of sinking particles reverses, indicating reentrainment into the mixed layer. A new theory is developed to model the gravitational settling flux when the particle concentration is nonuniform. The theory broadly agrees with the LES results and allows us to extend the analysis to a wider range of parameters.</jats:p

Predicting the microbial exposure risks in urban floods using GIS, building simulation, and microbial models

London is expected to experience more frequent periods of intense rainfall and tidal surges, leading to an increase in the risk of flooding. Damp and flooded dwellings can support microbial growth, including mould, bacteria, and protozoa, as well as persistence of flood-borne microorganisms. The amount of time flooded dwellings remain damp will depend on the duration and height of the flood, the contents of the flood water, the drying conditions, and the building construction, leading to particular properties and property types being prone to lingering damp and human pathogen growth or persistence. The impact of flooding on buildings can be simulated using Heat Air and Moisture (HAM) models of varying complexity in order to understand how water can be absorbed and dry out of the building structure. This paper describes the simulation of the drying of building archetypes representative of the English building stock using the EnergyPlus based tool ‘UCL-HAMT’ in order to determine the drying rates of different abandoned structures flooded to different heights and during different seasons. The results are mapped out using GIS in order to estimate the spatial risk across London in terms of comparative flood vulnerability, as well as for specific flood events. Areas of South and East London were found to be particularly vulnerable to long-term microbial exposure following major flood events

Needle Tip Force Estimation using an OCT Fiber and a Fused convGRU-CNN Architecture

Needle insertion is common during minimally invasive interventions such as biopsy or brachytherapy. During soft tissue needle insertion, forces acting at the needle tip cause tissue deformation and needle deflection. Accurate needle tip force measurement provides information on needle-tissue interaction and helps detecting and compensating potential misplacement. For this purpose we introduce an image-based needle tip force estimation method using an optical fiber imaging the deformation of an epoxy layer below the needle tip over time. For calibration and force estimation, we introduce a novel deep learning-based fused convolutional GRU-CNN model which effectively exploits the spatio-temporal data structure. The needle is easy to manufacture and our model achieves a mean absolute error of 1.76 +- 1.5 mN with a cross-correlation coefficient of 0.9996, clearly outperforming other methods. We test needles with different materials to demonstrate that the approach can be adapted for different sensitivities and force ranges. Furthermore, we validate our approach in an ex-vivo prostate needle insertion scenario.Comment: Accepted for Publication at MICCAI 201

The virtual maze: A behavioural tool for measuring trust

Trusting another person may depend on our level of generalised trust in others, as well as perceptions of that specific person's trustworthiness. However, many studies measuring trust outcomes have not discussed generalised versus specific trust. To measure specific trust in others, we developed a novel behavioural task. Participants navigate a virtual maze and make a series of decisions about how to proceed. Before each decision, they may ask for advice from two virtual characters they have briefly interviewed earlier. We manipulated the virtual characters' trustworthiness during the interview phase and measured how often participants approached and followed advice from each character. We also measured trust through ratings and an investment game. Across three studies we found participants followed advice from a trustworthy character significantly more than an untrustworthy character, demonstrating the validity of the maze task. Behaviour in the virtual maze reflected specific trust rather than generalised trust, whereas the investment game picked up on generalised trust as well as specific trust. Our data suggests the virtual maze task may provide an alternative behavioural approach to measuring specific trust in future research, and we demonstrate how the task may be used in traditional laboratories

Zinc transporter HKE4 as a new target in antihormone resistance of breast cancer

Background Oestrogen receptor-positive breast cancers develop resistance to anti-oestrogens by utilising alternative growth factor pathways as observed in our tamoxifen-resistant cell line (TAMR). These include EGFR, IGF1-R and Src signalling as well as increased growth and invasion. Zinc is elevated in breast cancer tissue and has been demonstrated to activate certain growth factor signalling pathways. We have tested the expression level of members of the LIV-1 family of zinc influx transporters and discovered that HKE4 (SLC39A7, ZIP7), previously shown by us capable of increasing the intracellular zinc levels, has increased expression in TAMR. We have therefore investigated whether the development of the more aggressive phenotype observed in our TAMR cells, including activation of these signalling pathways as well as increased growth and invasion, is due to an increase of intracellular zinc and as a direct result of increased expression of HKE4. Methods All nine members of the LIV-1 subfamily of ZIP transporters were measured in our model of tamoxifen-resistant breast cancer using Affymetrix arrays. Zinc-induced activation of growth factor signalling pathway components was investigated by western blot and/or fluorescent microscopy. Short-term (15-min) treatments with 20 μM zinc included ionophore, whereas long-term (hours/days) did not. Recombinant LIV-1 family members with a V5 tag were expressed using pcDNA3.1/V5-His-TOPO vector, and siRNA (Dharmacon smartpools with relevant controls) was used to reduce endogenous expression. Results HKE4 (SLC39A7), a ZIP transporter from the LIV-1 subfamily, was discovered to be elevated in TAMR cells by Affymetrix analysis and confirmed by PCR and western blot. We have observed that our TAMR cells have a twofold increase in intracellular zinc compared with wild-type cells, using the zinc-specific fluorescent dye Newport Green. Short-term zinc treatment of TAMR cells activates the signalling pathways implicated in antihormone-resistant proliferation and is reduced by both the zinc chelator TPEN and the Src kinase inhibitor SU6556. The same effects are observed after longer term (6 days) zinc treatment with additional increases in cell growth and invasion through Matrigel. Since we have previously demonstrated that HKE4 is capable of increasing intracellular zinc in cells and, more recently, that these TAMR have elevated intracellular zinc levels, we have tested the hypothesis that elevated HKE4 expression is directly responsible for the aggressive phenotype observed in our TAMR cells. Reducing HKE4 levels by siRNA demonstrated a role for this molecule in driving the zinc-induced activation of multiple signalling pathways. In the presence of siRNA for HKE4, the previously observed zinc-induced activation of EGFR, Src, and IGF1-R was eradicated and the EGF-stimulated activation was also decreased. Additionally, we have demonstrated the converse by transfecting recombinant HKE4 into wild-type cells and/or treating them with zinc to observe the activation of these signalling pathways and increases in invasive capability. Interestingly, we have observed a similar role of HKE4 in our model of faslodex-resistant breast cancer. Conclusion The presented results propose that HKE4, a member of the LIV-1 subfamily of ZIP transporters, is directly involved in the activation of the aggressive phenotype observed with the development of antihormone resistance, and as such is a potential new target for the prevention of resistance to antihormones in breast cancer progression

Generic, simple risk stratification model for heart valve surgery

BACKGROUND: Heart valve surgery has an associated in-hospital mortality rate of 4% to 8%. This study aims to develop a simple risk model to predict the risk of in-hospital mortality for patients undergoing heart valve surgery to provide information to patients and clinicians and to facilitate institutional comparisons.METHODS AND RESULTS: Data on 32 839 patients were obtained from the Society of Cardiothoracic Surgeons of Great Britain and Ireland on patients who underwent heart valve surgery between April 1995 and March 2003. Data from the first 5 years (n=16 679) were used to develop the model; its performance was evaluated on the remaining data ( n=16 160). The risk model presented here is based on the combined data. The overall in-hospital mortality was 6.4%. The risk model included, in order of importance (all P < 0.01), operative priority, age, renal failure, operation sequence, ejection fraction, concomitant tricuspid valve surgery, type of valve operation, concomitant CABG surgery, body mass index, preoperative arrhythmias, diabetes, gender, and hypertension. The risk model exhibited good predictive ability (Hosmer-Lemeshow test, P=0.78) and discriminated between high- and low-risk patients reasonably well (receiver-operating characteristics curve area, 0.77). CONCLUSIONS: This is the first risk model that predicts in-hospital mortality for aortic and/or mitral heart valve patients with or without concomitant CABG. Based on a large national database of heart valve patients, this model has been evaluated successfully on patients who had valve surgery during a subsequent time period. It is simple to use, includes routinely collected variables, and provides a useful tool for patient advice and institutional comparisons

Making the Case for “Whole System” Approaches Integrating Public Health and Housing

This is the final version. Available on open from MDPI via the DOI in this recordHousing conditions have been an enduring focus for public health activity throughout the modern public health era. However, the nature of the housing and health challenge has changed in response to an evolution in the understanding of the diverse factors influencing public health. Today, the traditional public health emphasis on the type and quality of housing merges with other wider determinants of health. These include the neighbourhood, community, and “place” where a house is located, but also the policies which make access to a healthy house possible and affordable for everyone. Encouragingly, these approaches to policy and action on housing have the potential to contribute to the “triple win” of health and well-being, equity, and environmental sustainability. However, more effective housing policies (and in public health in general) that adopt more systemic approaches to addressing the complex interactions between health, housing, and wider environment are needed. This paper illustrates some of the key components of the housing and health challenge in developed countries, and presents a conceptual model to co-ordinate activities that can deliver the “triple win.” This is achieved by offering a perspective on how to navigate more effectively, inclusively and across sectors when identifying sustainable housing interventions.This research was supported in part by funding provided by: (1) the South West Academic Health Science Network (grant number SW AHSN G005) and the European Regional Development Fund (grant number SZ07660) for the SMARTLINE Project; (2) the Eaga Charitable Trust; (3) the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Environmental Change and Health at the London School of Hygiene and Tropical Medicine in partnership with Public Health England, and in collaboration with the University of Exeter, University College London, and the Met Office; and (4) the European Commission Horizon 2020 funded INHERIT project, coordinated by EuroHealthNet (grant number 667364)