Safe Reinforcement Learning for Sepsis Treatment

Sepsis, a life-threatening illness, is estimated to be the primary cause of death for 50,000 people a year in the UK and many more worldwide. Managing the treatment of sepsis is very challenging as it is frequently missed, at an early stage, and the optimal treatment is not yet clear. There are promising attempts to use Reinforcement Learning (RL) to learn the optimal strategy to treat sepsis patients, especially for the administration of intravenous fluids and vasopressors. However, RL agents only take the current state of patients into account when recommending the dosage of vasopressors. This is inconsistent with current clinical safety practice in which the dosage of vasopressors is increased or decreased gradually. A sudden major change of the dosage might cause significant harm to patients and as such is considered unsafe in sepsis treatment. In this paper, we have adapted one of the deep RL methods published previously and evaluated it to assess whether it has this kind of sudden major change when recommending the vasopressor dosage. Then, we have modified this method to address the above safety constraint and learnt a safer policy by incorporating current clinical knowledge and practice

Pedagogical advantages of 3D virtual field trips and the challenges for their adoption

In a six-month long Innovate UK-funded project (November 2015 – April 2016), we investigated the feasibility of creating a sustainable national 3D ‘virtual field-trips’ (VFT) software service, to support and deliver field trip-based education through a virtual channel in schools and higher education institutions (HEIs). The idea of a 3D VFT service emerged from Virtual Skiddaw App, the 3D virtual geology fieldtrip, of The Open University’s (OU) Open Science Laboratory . In the feasibility project, we (at the OU) (co-investigator) along with Daden (project-lead) and Design Thinkers, UK (co-investigator) we looked into the technical, pedagogical, commercial and service design aspects of the 3D VFT service. In this presentation, we focussed on the pedagogy strand of this feasibility project: pedagogical advantages of 3D VFTs, and the challenges for their adoption in schools and HEIs. We discussed the following: pedagogical underpinnings of 3D virtual environments and 3D VFTs in disciplines such as geology, biology, environmental science/studies and geography which are founded on field observations, exploration and enquiry; potential of integrating VFTs within the curricula in schools and in HEIs; perceptions of educators, students and assessment bodies towards 3D VFTs, and virtual fieldwork, in general; we used the Virtual Skiddaw App in workshops and presentations to illustrate the concept of a 3D VFT; views of stakeholders towards the 3D VFT service: advantages, challenges and their requirements from this service. Our empirical investigations have been user-centred – focussing on the stakeholders and particularly, the end-users such as educators, students and fieldwork specialists, and we have interacted with them via interviews, service design workshops, demonstrations and a survey to elicit their perceptions and requirements

Final report on project SP1210: Lowland peatland systems in England and Wales – evaluating greenhouse gas fluxes and carbon balances

Lowland peatlands represent one of the most carbon-rich ecosystems in the UK. As a result of widespread habitat modification and drainage to support agriculture and peat extraction, they have been converted from natural carbon sinks into major carbon sources, and are now amongst the largest sources of greenhouse gas (GHG) emissions from the UK land-use sector. Despite this, they have previously received relatively little policy attention, and measures to reduce GHG emissions either through re-wetting and restoration or improved management of agricultural land remain at a relatively early stage. In part, this has stemmed from a lack of reliable measurements on the carbon and GHG balance of UK lowland peatlands. This project aimed to address this evidence gap via an unprecedented programme of consistent, multi year field measurements at a total of 15 lowland peatland sites in England and Wales, ranging from conservation managed ‘near-natural’ ecosystems to intensively managed agricultural and extraction sites. The use of standardised measurement and data analysis protocols allowed the magnitude of GHG emissions and removals by peatlands to be quantified across this heterogeneous data set, and for controlling factors to be identified. The network of seven flux towers established during the project is believed to be unique on peatlands globally, and has provided new insights into the processes the control GHG fluxes in lowland peatlands. The work undertaken is intended to support the future development and implementation of agricultural management and restoration measures aimed at reducing the contribution of these important ecosystems to UK GHG emissions

Understanding young people's transitions in university halls through space and time

This article contributes to the theoretical discussion about young people's transitions through space and time. Space and time are complex overarching concepts that have creative potential in deepening understanding of transition. The focus of this research is young people's experiences of communal living in university halls. It is argued that particular space-time concepts draw attention to different facets of experience and in combination deepen the understanding of young people's individual and collective transitions. The focus of the article is the uses of the space-time concepts 'routine', 'representation', 'rhythm' and 'ritual' to research young people's experiences. The article draws on research findings from two studies in the North of England. © 2010 SAGE Publications

Aquatic live animal radiotracing studies for ecotoxicological applications : addressing fundamental methodological deficiencies

The use of live animal gamma radioisotope tracer techniques in the field of ecotoxicology allows laboratory studies to accurately monitor contaminant biokinetics in real time for an individual organism. However, methods used in published studies for aquatic organisms are rarely described in sufficient detail to allow for study replication or an assessment of the errors associated with live animal radioanalysis to be identified. We evaluate the influence of some important methodological deficiencies through an overview of the literature on live aquatic animal radiotracer techniques and through the results obtained from our radiotracer studies on four aquatic invertebrate species. The main factors discussed are animal rinsing, radioanalysis and geometry corrections. We provide examples of three main techniques in live aquatic animal radiotracer studies to improve data quality control and demonstrate why each technique is crucial in interpreting the data from such studies. The animal rinsing technique is also relevant to non-radioisotope tracer studies, especially those involving nanoparticles. We present clear guidance on how to perform each technique and explain the importance of proper reporting of the validation of each technique for individual studies. In this paper we describe methods that are often used in lab-based radioecology studies but are rarely described in great detail. We hope that this paper will act as the basis for standard operating procedures for future radioecology studies to improve study replication and data quality control

A Functional Gene Array for Detection of Bacterial Virulence Elements

Emerging known and unknown pathogens create profound threats to public health. Platforms for rapid detection and characterization of microbial agents are critically needed to prevent and respond to disease outbreaks. Available detection technologies cannot provide broad functional information about known or novel organisms. As a step toward developing such a system, we have produced and tested a series of high-density functional gene arrays to detect elements of virulence and antibiotic resistance mechanisms. Our first generation array targets genes from Escherichia coli strains K12 and CFT073, Enterococcus faecalis and Staphylococcus aureus. We determined optimal probe design parameters for gene family detection and discrimination. When tested with organisms at varying phylogenetic distances from the four target strains, the array detected orthologs for the majority of targeted gene families present in bacteria belonging to the same taxonomic family. In combination with whole-genome amplification, the array detects femtogram concentrations of purified DNA, either spiked in to an aerosol sample background, or in combinations from one or more of the four target organisms. This is the first report of a high density NimbleGen microarray system targeting microbial antibiotic resistance and virulence mechanisms. By targeting virulence gene families as well as genes unique to specific biothreat agents, these arrays will provide important data about the pathogenic potential and drug resistance profiles of unknown organisms in environmental samples

Prevalence, predictors and perinatal outcomes of peri-conceptional alcohol exposure - retrospective cohort study in an urban obstetric population in Ireland

<p>Abstract</p> <p>Background</p> <p>Evidence-based advice on alcohol consumption is required for pregnant women and women planning a pregnancy. Our aim was to investigate the prevalence, predictors and perinatal outcomes associated with peri-conceptional alcohol consumption.</p> <p>Methods</p> <p>A cohort study of 61,241 women who booked for antenatal care and delivered in a large urban maternity hospital between 2000 and 2007. Self-reported alcohol consumption at the booking visit was categorised as low (0-5 units per week), moderate (6-20 units per week) and high (>20 units per week).</p> <p>Results</p> <p>Of the 81% of women who reported alcohol consumption during the peri-conceptional period, 71% reported low intake, 9.9% moderate intake and 0.2% high intake. Factors associated with moderate alcohol consumption included being in employment OR 4.47 (95% CI 4.17 to 4.80), Irish nationality OR 16.5 (95% CI 14.9 to 18.3), private health care OR 5.83 (95% CI 5.38 to 6.31) and smoking OR 1.86 (95% CI 1.73 to 2.01). Factors associated with high consumption included maternal age less than 25 years OR 2.70 (95% CI 1.86 to 3.91) and illicit drug use OR 6.46 (95% CI 3.32 to 12.60). High consumption was associated with very preterm birth (<32 weeks gestation) even after controlling for socio-demographic factors, adjusted OR 3.15 (95% CI 1.26-7.88). Only three cases of Fetal Alcohol Syndrome were recorded (0.05 per 1000 total births), one each in the low, moderate and high consumption groups.</p> <p>Conclusions</p> <p>Public Health campaigns need to emphasise the importance of peri-conceptional health and pre-pregnancy planning. Fetal Alcohol Syndrome is likely to be under-reported despite the high prevalence of alcohol consumption in this population.</p

National disability-adjusted life years(DALYs) for 257 diseases and injuries in Ethiopia, 1990–2015: findings from the global burden of disease study 2015

Background: Disability-adjusted life years (DALYs) provide a summary measure of health and can be a critical input to guide health systems, investments, and priority-setting in Ethiopia. We aimed to determine the leading causes of premature mortality and disability using DALYs and describe the relative burden of disease and injuries in Ethiopia. Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for non-fatal disease burden, cause-specific mortality, and all-cause mortality to derive age-standardized DALYs by sex for Ethiopia for each year. We calculated DALYs by summing years of life lost due to premature mortality (YLLs) and years lived with disability (YLDs) for each age group and sex. Causes of death by age, sex, and year were measured mainly using Causes of Death Ensemble modeling. To estimate YLDs, a Bayesian meta-regression method was used. We reported DALY rates per 100,000 for communicable, maternal, neonatal, and nutritional (CMNN) disorders, non-communicable diseases, and injuries, with 95% uncertainty intervals (UI) for Ethiopia. Results: Non-communicable diseases caused 23,118.1 (95% UI, 17,124.4–30,579.6), CMNN disorders resulted in 20,200.7 (95% UI, 16,532.2–24,917.9), and injuries caused 3781 (95% UI, 2642.9–5500.6) age-standardized DALYs per 100,000 in Ethiopia in 2015. Lower respiratory infections, diarrheal diseases, and tuberculosis were the top three leading causes of DALYs in 2015, accounting for 2998 (95% UI, 2173.7–4029), 2592.5 (95% UI, 1850.7–3495.1), and 2562.9 (95% UI, 1466.1–4220.7) DALYs per 100,000, respectively. Ischemic heart disease and cerebrovascular disease were the fourth and fifth leading causes of age-standardized DALYs, with rates of 2535.7 (95% UI, 1603.7–3843.2) and 2159.9 (95% UI, 1369.7–3216.3) per 100,000, respectively. The following causes showed a reduction of 60% or more over the last 25 years: lower respiratory infections, diarrheal diseases, tuberculosis, neonatal encephalopathy, preterm birth complications, meningitis, malaria, protein-energy malnutrition, iron-deficiency anemia, measles, war and legal intervention, and maternal hemorrhage

A mobile phone-based care model for outpatient cardiac rehabilitation: the care assessment platform (CAP)

<p>Abstract</p> <p>Background</p> <p>Cardiac rehabilitation programs offer effective means to prevent recurrence of a cardiac event, but poor uptake of current programs have been reported globally. Home based models are considered as a feasible alternative to avoid various barriers related to care centre based programs. This paper sets out the study design for a clinical trial seeking to test the hypothesis that these programs can be better and more efficiently supported with novel Information and Communication Technologies (ICT).</p> <p>Methods/Design</p> <p>We have integrated mobile phones and web services into a comprehensive home- based care model for outpatient cardiac rehabilitation. Mobile phones with a built-in accelerometer sensor are used to measure physical exercise and WellnessDiary software is used to collect information on patients' physiological risk factors and other health information. Video and teleconferencing are used for mentoring sessions aiming at behavioural modifications through goal setting. The mentors use web-portal to facilitate personal goal setting and to assess the progress of each patient in the program. Educational multimedia content are stored or transferred via messaging systems to the patients phone to be viewed on demand. We have designed a randomised controlled trial to compare the health outcomes and cost efficiency of the proposed model with a traditional community based rehabilitation program. The main outcome measure is adherence to physical exercise guidelines.</p> <p>Discussion</p> <p>The study will provide evidence on using mobile phones and web services for mentoring and self management in a home-based care model targeting sustainable behavioural modifications in cardiac rehabilitation patients.</p> <p>Trial registration</p> <p>The trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with number ACTRN12609000251224.</p

Mutations in Wnt2 Alter Presynaptic Motor Neuron Morphology and Presynaptic Protein Localization at the Drosophila Neuromuscular Junction

Wnt proteins are secreted proteins involved in a number of developmental processes including neural development and synaptogenesis. We sought to determine the role of the Drosophila Wnt7b ortholog, Wnt2, using the neuromuscular junction (NMJ). Mutations in wnt2 produce an increase in the number of presynaptic branches and a reduction in immunolabeling of the active zone proteins, Bruchpilot and synaptobrevin, at the NMJ. There was no change, however, in immunolabeling for the presynaptic proteins cysteine-string protein (CSP) and synaptotagmin, nor the postsynaptic proteins GluRIIA and DLG at the NMJ. Consistent with the presynaptic defects, wnt2 mutants exhibit approximately a 50% reduction in evoked excitatory junctional currents. Rescue, RNAi, and tissue-specific qRT-PCR experiments indicate that Wnt2 is expressed by the postsynaptic cell where it may serve as a retrograde signal that regulates presynaptic morphology and the localization of presynaptic proteins