Capturing the time-varying drivers of an epidemic using stochastic dynamical systems

Epidemics are often modelled using non-linear dynamical systems observed through partial and noisy data. In this paper, we consider stochastic extensions in order to capture unknown influences (changing behaviors, public interventions, seasonal effects etc). These models assign diffusion processes to the time-varying parameters, and our inferential procedure is based on a suitably adjusted adaptive particle MCMC algorithm. The performance of the proposed computational methods is validated on simulated data and the adopted model is applied to the 2009 H1N1 pandemic in England. In addition to estimating the effective contact rate trajectories, the methodology is applied in real time to provide evidence in related public health decisions. Diffusion driven SEIR-type models with age structure are also introduced.Comment: 21 pages, 5 figure

Effect of Water Content on the Thermal Inactivation Kinetics of Horseradish Peroxidase Freeze-Dried from Alkaline pH

The thermal inactivation of horseradish peroxidase freeze-dried from solutions of different pH (8, 10 and 11.5, measured at 25 C) and equilibrated to different water contents was studied in the temperature range from 110 to 150 C. The water contents studied (0.0, 1.4, 16.2 and 25.6 g water per 100 g of dry enzyme) corresponded to water activities of 0.0, 0.11, 0.76 and 0.88 at 4 C. The kinetics were well described by a double exponential model. The enzyme was generally more stable the lower the pH of the original solution, and for all pH values, the maximum stability was obtained at 1.4 g water/100 g dry enzyme. Values of z were generally independent of water content and of the pH of the original solution, and in the range of 15–25 °C, usually found in neutral conditions, with the exception of the enzyme freeze dried from pH 11.5 and equilibrated with phosphorus pentoxide, where a z-value of the stable fraction close to 10 C was found

Patterns of symptoms possibly indicative of cancer and associated help-seeking behaviour in a large sample of United Kingdom residents - the USEFUL study

Background.Cancer awareness campaigns aim to increase awareness of the potential seriousness of signs and symptoms of cancer, and encourage their timely presentation to healthcare services. Enhanced understanding of the prevalence of symptoms possibly indicative of cancer in different population subgroups, and associated general practitioner (GP) help-seeking behaviour, will help to target cancer awareness campaigns more effectively.Aim.To determine: i) the prevalence of 21 symptoms possibly indicative of breast, colorectal, lung or upper gastrointestinal cancer in the United Kingdom (UK), including six ‘red flag’ symptoms; ii) whether the prevalence varies among population subgroups; iii) the proportion of symptoms self-reported as presented to GPs; iv) whether GP help-seeking behaviour varies within population subgroups.Methods.Self-completed questionnaire about experience of, and response to, 25 symptoms (including 21 possibly indicative of the four cancers of interest) in the previous month and year; sent to 50,000 adults aged 50 years or more and registered with 21 general practices in Staffordshire, England or across Scotland. Results.Completed questionnaires were received from 16,778 respondents (corrected response rate 34.2%). Almost half (45.8%) of respondents had experienced at least one symptom possibly indicative of cancer in the last month, and 58.5% in the last year. The prevalence of individual symptoms varied widely (e.g. in the last year between near zero% (vomiting up blood) and 15.0% (tired all the time). Red flag symptoms were uncommon. Female gender, inability to work because of illness, smoking, a history of a specified medical diagnosis, low social support and lower household income were consistently associated with experiencing at least one symptom possibly indicative of cancer in both the last month and year. The proportion of people who had contacted their GP about a symptom experienced in the last month varied between 8.1% (persistent cough) and 39.9% (unexplained weight loss); in the last year between 32.8% (hoarseness) and 85.4% (lump in breast). Nearly half of respondents experiencing at least one red flag symptom in the last year did not contact their GP about it. Females, those aged 80+ years, those unable to work because of illness, ex-smokers and those previously diagnosed with a specified condition were more likely to report a symptom possibly indicative of cancer to their GP; and those on high household income less likely.Conclusion.Symptoms possibly indicative of cancer are common among adults aged 50+ years in the UK, although they are not evenly distributed. Help-seeking responses to different symptoms also vary. Our results suggest important opportunities to provide more nuanced messaging and targeting of symptom-based cancer awareness campaigns

Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999-2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies-one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation

There and back again: detecting regularity in human encounter communities

Detecting communities that recur over time is a challenging problem due to the potential sparsity of encounter events at an individual scale and inherent uncertainty in human behavior. Existing methods for community detection in mobile human encounter networks ignore the presence of temporal patterns that lead to periodic components in the network. Daily and weekly routine are prevalent in human behavior and can serve as rich context for applications that rely on person-to-person encounters, such as mobile routing protocols and intelligent digital personal assistants. In this article, we present the design, implementation, and evaluation of an approach to decentralized periodic community detection that is robust to uncertainty and computationally efficient. This alternative approach has a novel periodicity detection method inspired by a neural synchrony measure used in the field of neurophysiology. We evaluate our approach and investigate human periodic encounter patterns using empirical datasets of inferred and direct-sensed encounters

Molecular Basis of Prostate Cancer Diagnostics and Therapeutics

Prostate Cancer is now the second biggest cause of cancer mortality in the UK. Media coverage has been rising, with some attributing to a rise in the cases diagnosed and treated in the NHS down to the “Fry and Turnbull effect”. Our understanding of prostate cancer has increased tremendously in the past decades, with advances in molecular biology and genomics driving the way to new treatments and diagnostics. This Special Edition of Translational Andrology and Urology 2019: Prostate Cancer Biology and Genomics aims to review the current state of prostate cancer genomics, proteomics, diagnostics and treatment

N-(3,4-Dichloro­phen­yl)-3-oxo­butanamide

In the title compound. C10H9Cl2NO2, the acetamide residue is twisted out of the phenyl ring plane by 25.40 (9)°. An intra­molecular C—H⋯O close contact is observed. The N atom of the butanamide unit forms an inter­molecular N—H⋯O hydrogen bond with the symmetry-related carbonyl O atom, inter­linking mol­ecules into a C(4) chain along [100]. Additional C—H⋯O inter­molecular inter­actions and Cl⋯Cl contacts [3.4364 (8) Å] contribute to the stability of the crystal packing

Using Defence Engagement (Health) to progress the Women Peace and Security agenda

Since the unanimous passing of United Nations Security Council Resolution 1325, which calls on member states to address gender inequality, many countries and the wider North Atlantic Treaty Organisation community have championed the Women Peace and Security agenda to empower women and reduce violence within fragile states. When women are empowered and actively involved in decision-making, there is less violence, and more peace and stability in that society, which benefits all members.Defence Medical Services are uniquely positioned to progress this agenda, particularly through its Defence Engagement activities. The UK’s military medical community has more women in leadership than the wider military community. Our personnel can and should be used to model and empower military healthcare workers in partner nations. This paper forms part of a special issue of BMJ Military Health dedicated to Defence Engagement

Decoupled Programs, Payment Incidence, and Factor Markets: Evidence from Market Experiments

We use laboratory market experiments to assess the impact of asymmetric knowledge of a per-unit subsidy and the effect of a decoupled annual income subsidy on factor market outcomes. Results indicate that when the subsidy is tied to the factor as a per-unit subsidy, regardless of full or asymmetric knowledge for market participants, subsidized factor buyers distribute nearly 22 percent of the subsidy to factor sellers. When the subsidy is fully decoupled from the factor, as is the case with the annual payment, payment incidence is mitigated and prices are not statistically different from the no-policy treatment.laboratory market experiments, agricultural subsidies, subsidy incidence, land market, ex ante policy analysis, Agricultural and Food Policy, Institutional and Behavioral Economics, Q18, D03, C92,