Epidemiology: a tool for the assessment of risk

The purpose of this chapter is to introduce and demonstrate the use of a key tool for the assessment of risk. The word epidemiology is derived from Greek and its literal interpretation is 'studies of people'. A more usual definition, however is the scientific study of disease patters among populations in time and space. This chapter introduces some of the techniques used in epidemiology studies and illustrates their uses in the evaluation or setting of microbiological guidelines for recreational water, wastewater reuse and drinking water

Transmission of Schistosoma haematobium in seasonal pools in the Gambia, with particular reference to the role of human contact

The transmission of S. haematobium in seasonal pools in The Gambia was investigated during the 1982 and 1983 transmission seasons. Studies were carried out on (a) infections in the snail intermediate host, Bulinus senegalensis, (b) cercarial densities in the pools, (c) water contact behaviour at the pools, and (d) the pattern of human infection. It was found that seasonal changes in the pools influenced both the snail populatons and the water contact patterns. Snail infection rates were low overall but were high in particular months and pools. Most infections occurred in one pool (maximum monthly mean infection rate 5.9%). Field and laboratory studies indicated that high mortality of B. senegalensis was counteracted by a high intrinsic rate of natural increase, and transmission of S. haematobium was maintained by a short prepatent period of the parasite. The cercariometric technique used had a 74% recovery accuracy in the laboratory. Cercarial densities in the pools were generally below 1 cercaria/litre, and the maximum density was 5.8 c/1. Cercarial densities were highest around midday, close to the vegetation in the middle of the pool as the pools were drying out. Transmission potential, as measured by cercarial density, varied between contact sites, months, times of day and position within a site. Human water contact was monitored by direct observation using a new "time-point" method and by recording frequency and duration of water contact of individuals. The observed activities were mainly for domestic and recreational purposes. Water contact was focal and seasonal, and the exposure potential (product of cercarial density and duration of contact at each pool) was highest at two pools and in the latter half of the season. The amount of water contact varied markedly between sexes and age groups. Contact increased progressively between ages 2-9 years, remaining at very high levels in females over the age of 10 years but declining to low levels in adult males. Substantial variation occurred in the contact of individuals in a narrow age group. An index of individual exposure to infection was calculated for two cohorts, aged 8-13 years and 2-70 years, by modifying the duration of contact by each individual by factors for the cercarial density at the pool used and for the activity performed. The resultant pattern of exposure to infection was markedly different from the pattern of duration of water contact: in particular, the mean exposure of adult women was reduced to less than that of children, although individual adult women had higher exposure levels than some children. The intensity of S. haematobium infection was highest in children aged 5-14 years and declined to low levels in adults. In 2-14 year olds increased exposure to infection was associated with an increase in reinfection after treatment. Adults had low levels of both infection and reinfection, although some had high levels of exposure to infection. It is concluded that both exposure and age influenced the pattern of infection in the community. The combined results of these studies indicates the complexity of transmission of schistosomiasis from snail to man, and shows that contact to very low cercarial densities can result in high levels of human infection

Single-parameter non-adiabatic quantized charge pumping

Controlled charge pumping in an AlGaAs/GaAs gated nanowire by single-parameter modulation is studied experimentally and theoretically. Transfer of integral multiples of the elementary charge per modulation cycle is clearly demonstrated. A simple theoretical model shows that such a quantized current can be generated via loading and unloading of a dynamic quasi-bound state. It demonstrates that non-adiabatic blockade of unwanted tunnel events can obliterate the requirement of having at least two phase-shifted periodic signals to realize quantized pumping. The simple configuration without multiple pumping signals might find wide application in metrological experiments and quantum electronics.Comment: 4 pages, 4 figure

Inverse Compton Scattering as the Source of Diffuse EUV Emission in the Coma Cluster of Galaxies

We have examined the hypothesis that the majority of the diffuse EUV flux in the Coma cluster is due to inverse Compton scattering of low energy cosmic ray electrons (0.16 < epsilon < 0.31 GeV) against the 3K black-body background. We present data on the two-dimensional spatial distribution of the EUV flux and show that these data provide strong support for a non-thermal origin for the EUV flux. However, we show that this emission cannot be produced by an extrapolation to lower energies of the observed synchrotron radio emitting electrons and an additional component of low energy cosmic ray electrons is required.Comment: 11 pages, 5 figure

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Prolonged podocyte depletion in larval zebrafish resembles mammalian focal and segmental glomerulosclerosis

Focal and segmental glomerulosclerosis (FSGS) is a histological pattern frequently found in patients with nephrotic syndrome that often progress to end-stage kidney disease. The initial step in development of this histologically defined entity is injury and ultimately depletion of podocytes, highly arborized interdigitating cells on the glomerular capillaries with important function for the glomerular filtration barrier. Since there are still no causal therapeutic options, animal models are needed to develop new treatment strategies. Here, we present an FSGS-like model in zebrafish larvae, an eligible vertebrate model for kidney research. In a transgenic zebrafish strain, podocytes were depleted, and the glomerular response was investigated by histological and morphometrical analysis combined with immunofluorescence staining and ultrastructural analysis by transmission electron microscopy. By intravenous injection of fluorescent high-molecular weight dextran, we confirmed leakage of the size selective filtration barrier. Additionally, we observed severe podocyte foot process effacement of remaining podocytes, activation of proximal tubule-like parietal epithelial cells identified by ultrastructural cytomorphology, and expression of proximal tubule markers. These activated cells deposited extracellular matrix on the glomerular tuft which are all hallmarks of FSGS. Our findings indicate that glomerular response to podocyte depletion in larval zebrafish resembles human FSGS in several important characteristics. Therefore, this model will help to investigate the disease development and the effects of potential drugs in a living organism

Simultaneous X-ray spectroscopy of YY Gem with Chandra and XMM-Newton

We report on a detailed study of the X-ray spectrum of the nearby eclipsing spectroscopic binary YY Gem. Observations were obtained simultaneously with both large X-ray observatories, XMM-Newton and Chandra. We compare the high-resolution spectra acquired with the Reflection Grating Spectrometer onboard XMM-Newton and with the Low Energy Transmission Grating Spectrometer onboard Chandra, and evidence in direct comparison the good performance of both instruments in terms of wavelength and flux calibration. The strongest lines in the X-ray spectrum of YY Gem are from oxygen. Oxygen line ratios indicate the presence of a low-temperature component (1-4 MK) with density n_e < 2 10^{10} cm^-3. The X-ray lightcurve reveals two flares and a dip corresponding to the secondary eclipse. An increase of the density during phases of high activity is suggested from time-resolved spectroscopy. Time-resolved global fitting of the European Photon Imaging Camera CCD spectrum traces the evolution of temperature and emission measure during the flares. These medium-resolution spectra show that temperatures > 10^7 K are relevant in the corona of YY Gem although not as dominant as the lower temperatures represented by the strongest lines in the high-resolution spectrum. Magnetic loops with length on the order of 10^9 cm, i.e., about 5 % of the radius of each star, are inferred from a comparison with a one-dimensional hydrodynamic model. This suggests that the flares did not erupt in the (presumably more extended) inter-binary magnetosphere but are related to one of the components of the binary.Comment: 15 pages, accepted for publication in A&

Partitioning of on-demand electron pairs

We demonstrate the high fidelity splitting of electron pairs emitted on demand from a dynamic quantum dot by an electronic beam splitter. The fidelity of pair splitting is inferred from the coincidence of arrival in two detector paths probed by a measurement of the partitioning noise. The emission characteristic of the on-demand electron source is tunable from electrons being partitioned equally and independently to electron pairs being split with a fidelity of 90%. For low beam splitter transmittance we further find evidence of pair bunching violating statistical expectations for independent fermions

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

Background The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. Methods Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. Results Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s−1 (P<0.01), and F-wave latency was 7.7 (0.5) vs 7.0 (0.2) ms (P<0.01), respectively. Motor nerve block duration was prolonged in late diabetic animals, but neurotoxicity was not. Late diabetic animals receiving insulin showed intermediate results. Conclusions In a rodent type II DM model, nerves have increased sensitivity for short-acting local anaesthetics without adjuvants in vivo, as evidenced by prolonged block duration. This sensitivity appears to increase with the progression of neuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve bloc

Two refreshing views of Fluctuation Theorems through Kinematics Elements and Exponential Martingale

In the context of Markov evolution, we present two original approaches to obtain Generalized Fluctuation-Dissipation Theorems (GFDT), by using the language of stochastic derivatives and by using a family of exponential martingales functionals. We show that GFDT are perturbative versions of relations verified by these exponential martingales. Along the way, we prove GFDT and Fluctuation Relations (FR) for general Markov processes, beyond the usual proof for diffusion and pure jump processes. Finally, we relate the FR to a family of backward and forward exponential martingales.Comment: 41 pages, 7 figures; version2: 45 pages, 7 figures, minor revisions, new results in Section