New parametrization method for dissipative particle dynamics

We introduce an improved method of parameterizing the Groot-Warren version of Dissipative Particle Dynamics (DPD) by exploiting a correspondence between DPD and Scatchard-Hildebrand regular solution theory. The new parameterization scheme widens the realm of applicability of DPD by first removing the restriction of equal repulsive interactions between like beads, and second, by relating all conservative interactions between beads directly to cohesive energy densities. We establish the correspondence by deriving an expression for the Helmoltz free energy of mixing obtaining a heat of mixing which is exactly the same form as that for a regular mixture (quadratic in the volume fraction) and an entropy of mixing which reduces to the ideal entropy of mixing for equal molar volumes. We equate the conservative interaction parameters in the DPD force law to the cohesive energy densities of the pure fluids providing an alternative method of calculating the self-interaction parameters as well as a route to the cross-interaction parameter. We validate the new parameterization by modelling the binary system: SnI4/SiCl4, which displays liquid-liquid coexistence below an upper critical solution temperature around 140°C. A series of DPD simulations were conducted at a set of temperatures ranging from 0°C to above the experimental upper critical solution temperature using conservative parameters based on extrapolated experimental data. These simulations can be regarded as being equivalent to a quench from a high temperature to a lower one at constant volume. Our simulations recover the expected phase behaviour ranging from solid-liquid coexistence to liquid-liquid co-existence and eventually leading to a homogeneous single phase system. The results yield a binodal curve in close agreement with one predicted using regular solution theory, but, significantly, in closer agreement with actual solubility measurements

The Relationship Between Grit and Physical Activity in Primigravida and Multigravida Pregnant Women

Physical activity (PA) levels decline when women become pregnant; this may differ by gravidity (number of pregnancies). Grit is a construct consisting of two facets including perseverance of effort (perseverance) and consistency of interest (consistency), and it may be predictive of PA volume and/or intensity in individuals. PURPOSE: To determine the relationship between grit and PA levels of various activity types in pregnant women, including assessing primigravida and multigravida women. METHODS: Pregnant women (n=126; 27.6 years old; 17.7 weeks gestation) in Utah, USA were assessed for grit (overall score and the consistency and perseverance facets) with the Short Grit Scale (Grit-S) and for PA levels across various activity types with the Pregnancy Physical Activity Questionnaire (PPAQ). Pearson’s correlation coefficients (r) were used to assess the strength of the relationships between grit and prenatal PA. Unpaired t-tests were used to compare primigravida and multigravida data. RESULTS: Overall grit and the consistency facet were not significantly (p \u3e 0.05) related to any of the PA types measured. No significant differences were found in grit (overall and consistency and perseverance facets) between primigravida and multigravida women. In contrast, the perseverance facet of grit had a significant (p \u3c 0.05) weak inverse relationship between moderate-intensity (r = -0.22), household/caregiving (r = -0.20), moderate + vigorous (r = -0.22), and total PA (r = -0.20) with no significant relationships with the other activity types (r range: 0.05 - -0.15). Further, compared to multigravida women, primigravida mothers had significantly higher weekly sedentary and occupational PA, yet they had lower weekly light-intensity and household/caregiving PA, with no differences in the other activity types including moderate + vigorous and total activity. CONCLUSION: These findings are the first evidence for the relationship between the perseverance of effort facet of grit and weekly PA levels in pregnant women. Further, we add support to existing literature that PA levels may vary by gravidity and should be considered when developing PA interventions in pregnant women. Findings from this study can be used to tailor programs by gravidity to help women meet the prenatal PA guidelines

B-type natriuretic peptide-guided treatment for heart failure

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT‐proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP‐guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow‐up. Adults treated for heart failure, in both in‐hospital and out‐of‐hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP‐guided treatment with clinical assessment alone. The evidence for all‐cause mortality using NP‐guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence). The evidence suggested heart failure admission was reduced by NP‐guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all‐cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence). Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP‐guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD ‐0.03, 95% CI ‐1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence). We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. Authors' conclusions In patients with heart failure low‐quality evidence showed a reduction in heart failure admission with NP‐guided treatment while low‐quality evidence showed uncertainty in the effect of NP‐guided treatment for all‐cause mortality, heart failure mortality, and all‐cause admission. Uncertainty in the effect was further shown by very low‐quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.</p

Phase evolution of slag-rich cementitious grouts for immobilisation of nuclear wastes

An updated calcium silicate hydrate (C–S–H) model incorporating aluminium-containing end-members was used for thermodynamic modelling of blended cements using blast-furnace slag and Portland cement (BFS:PC) with ratios of 1:1, 3:1 and 9:1, using GEMSelektor. Selective dissolution and magic angle spinning nuclear magnetic resonance (MAS NMR) studies were performed to determine the degree of hydration (DoH) of the anhydrous material as an input parameter for the modelling work. Both techniques showed similar results for determining the DoH of the BFS within each sample. Characterisation of the hardened cement pastes over 360 days, using X-ray diffraction analysis and MAS NMR, demonstrated that the use of the updated C–S–H model can highlight the effect of different blend ratios and curing ages on the phase assemblages in these cements. Validation using this modelling approach was performed on 20 year old specimens from the literature to highlight its applicability for modelling later-age blended cements

Thermodynamic modelling of BFS-PC cements under temperature conditions relevant to the geological disposal of nuclear wastes

Intermediate level waste produced in UK nuclear power generation is encapsulated or immobilised in blended cements comprising blast furnace slag (BFS) and Portland cement (PC), to be emplaced in a proposed geological disposal facility (GDF). The wasteforms are expected to be exposed to temperatures from 35 to 80 °C during the initial 150 years of GDF operation. Thermodynamic modelling is applied here to describe the phase assemblages of hydrated 1:1, 3:1 and 9:1 BFS-PC blends, with the participation of hydrogarnet as an important phase above 60 °C. The chemical composition of the main phase forming in these systems, an aluminium rich calcium silicate hydrate (C-A-S-H), was well described by a solid-solution model with explicit Al incorporation, although the Al/Si ratio was systematically slightly under-predicted. The developed thermodynamic model predicts the correct phase assemblage across varying temperature regimes, making it a valuable tool to assess the effects of temperature on cements

CASNET2: Evaluation of an Electronic Safety Netting cancer toolkit for the primary care electronic health record: protocol for a pragmatic stepped-wedge RCT

Introduction: Safety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices. A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web. Methods and analysis: We will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation. Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant. Ethics and dissemination: Ethical approval has been obtained from the North West—Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites

Risk factors for influenza-related complications in children during the 2009/10 pandemic: a UK primary care cohort study using linked routinely collected data.

Primary care clinicians have a central role in managing influenza/influenza-like illness (ILI) during influenza pandemics. This study identifies risk factors for influenza-related complications in children presenting with influenza/ILI in primary care. We conducted a cohort study using routinely collected linked data from the Clinical Practice Research Datalink on children aged 17 years and younger who presented with influenza/ILI during the 2009/10 pandemic. We calculated odds ratios (ORs) for potential risk factors in relation to influenza-related complications, complications requiring intervention, pneumonia, all-cause hospitalisation and hospitalisation due to influenza-related complications within 30 days of presentation. Analyses were adjusted for potential confounders including age, vaccination and socio-economic deprivation. Asthma was a risk factor for influenza-related complications (adjusted OR 1.48, 95% confidence interval (CI) 1.21-1.80, P < 0.001), complications requiring intervention (adjusted OR 1.44, 95% CI 1.11-1.88; P = 0.007), pneumonia (adjusted OR 1.64, 95% CI 1.07-2.51, P = 0.024) and hospitalisation due to influenza-related complications (adjusted OR 2.46, 95% CI 1.09-5.56, P = 0.031). Neurological conditions were risk factors for all-cause hospitalisation (adjusted OR 4.25, 95% CI 1.50-12.07, P = 0.007) but not influenza-related complications (adjusted OR 1.46, 95% CI 0.83-2.56, P = 0.189). Community-based early interventions to prevent influenza-related clinical deterioration should therefore be primarily targeted at children with asthma and neurological conditions

Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care

Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses