Bayesian analysis for inference of an emerging epidemic: citrus canker in urban landscapes.

Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics.FMN gratefully acknowledges financial support from BBSRC, USDA-ARS, USDA-Aphis PPQ, Citrus Research and Development Foundation. CAG gratefully acknowledges the support of a BBSRC Professorial Fellowship, with additional support from USDA and Defra. ARC was supported by BBSRC, USDA, the National University of Singapore, and NMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A Computation in a Cellular Automaton Collider Rule 110

A cellular automaton collider is a finite state machine build of rings of one-dimensional cellular automata. We show how a computation can be performed on the collider by exploiting interactions between gliders (particles, localisations). The constructions proposed are based on universality of elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and computing on rings.Comment: 39 pages, 32 figures, 3 table

The precision of textural analysis in 18F-FDG-PET scans of oesophageal cancer

Objectives: Measuring tumour heterogeneity by textural analysis in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) provides predictive and prognostic information but technical aspects of image processing can influence parameter measurements. We therefore tested effects of image smoothing, segmentation and quantisation on the precision of heterogeneity measurements. Methods: Sixty-four 18F-FDG PET/CT images of oesophageal cancer were processed using different Gaussian smoothing levels (2.0, 2.5, 3.0, 3.5, 4.0 mm), maximum standardised uptake value (SUVmax) segmentation thresholds (45 %, 50 %, 55 %, 60 %) and quantisation (8, 16, 32, 64, 128 bin widths). Heterogeneity parameters included grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRL), neighbourhood grey-tone difference matrix (NGTDM), grey-level size zone matrix (GLSZM) and fractal analysis methods. The concordance correlation coefficient (CCC) for the three processing variables was calculated for each heterogeneity parameter. Results: Most parameters showed poor agreement between different bin widths (CCC median 0.08, range 0.004–0.99). Segmentation and smoothing showed smaller effects on precision (segmentation: CCC median 0.82, range 0.33–0.97; smoothing: CCC median 0.99, range 0.58–0.99). Conclusions: Smoothing and segmentation have only a small effect on the precision of heterogeneity measurements in 18F-FDG PET data. However, quantisation often has larger effects, highlighting a need for further evaluation and standardisation of parameters for multicentre studies. Key points: • Heterogeneity measurement precision in 18 F-FDG PET is influenced by image processing methods. • Quantisation shows large effects on precision of heterogeneity parameters in 18 F-FDG PET/CT. • Smoothing and segmentation show comparatively smaller effects on precision of heterogeneity parameters

Simple networks on complex cellular automata: From de Bruijn diagrams to jump-graphs

We overview networks which characterise dynamics in cellular automata. These networks are derived from one-dimensional cellular automaton rules and global states of the automaton evolution: de Bruijn diagrams, subsystem diagrams, basins of attraction, and jump-graphs. These networks are used to understand properties of spatially-extended dynamical systems: emergence of non-trivial patterns, self-organisation, reversibility and chaos. Particular attention is paid to networks determined by travelling self-localisations, or gliders.Comment: 25 pages, 14 figure

Influence of speed of sample processing on placental energetics and signalling pathways: implications for tissue collection.

INTRODUCTION: The placenta is metabolically highly active due to extensive endocrine and active transport functions. Hence, placental tissues soon become ischaemic after separation from the maternal blood supply. Ischaemia rapidly depletes intracellular ATP, and leads to activation of stress-response pathways aimed at reducing metabolic demands and conserving energy resources for vital functions. Therefore, this study aimed to elucidate the effects of ischaemia ex vivo as may occur during tissue collection on phosphorylation of placental proteins and kinases involved in growth and cell survival, and on mitochondrial complexes. METHODS: Eight term placentas obtained from normotensive non-laboured elective caesarean sections were kept at room-temperature and sampled at 10, 20, 30 and 45 min after delivery. Samples were analyzed by Western blotting. RESULTS: Between 10 and 45 min the survival signalling pathway intermediates, P-AKT, P-GSK3α and β, P-4E-BP1 and P-p70S6K were reduced by 30-65%. Stress signalling intermediates, P-eIF2α increased almost 3 fold after 45 min. However, other endoplasmic reticulum stress markers and the Heat Shock Proteins, HSP27, HSP70 and HSP90, did not change. Phosphorylation of AMPK, an energy sensor, was elevated 2 fold after 45 min. Contemporaneously, there was an ∼25% reduction in mitochondrial complex IV subunit I. DISCUSSION AND CONCLUSIONS: These results suggest that for placental signalling studies, samples should be taken and processed within 10 min of caesarean delivery to minimize the impact of ischaemia on protein phosphorylation

Comparison of SPECT bone scintigraphy with MRI for diagnosis of meniscal tears

BACKGROUND: Scintigraphy has been considered as competitive to MRI, but limited data are available on the accuracy of single photon emission tomography (SPECT) compared with MRI for the assessment of meniscal tears. Our objective was to assess the value of SPECT in comparison to MRI. METHODS: Between January 2003 and March 2004, sixteen patients were studied with both modalities and the accuracy rates of SPECT scan results, and MRI findings in the diagnosis of meniscal tears were compared. Arthroscopy was the gold standard. RESULTS: The respective sensitivity rate, specificity rate, and positive and negative predictive accuracies of MRI were 89%, 94%, 93%, and 79% and for SPECT those were 78%, 94%, 94%, and 88%. There was good agreement on the presence or absence of tears between two modalities (κ statistic = 0.699). CONCLUSION: SPECT and MRI are both valuable imaging techniques. SPECT is a useful alternative when MRI is unavailable or unsuitable and it is beneficial when more possible accuracy is desired (such as when MRI results are either inconclusive or conflict with other clinical data)

Factors Affecting a Recently Purchased Handgun’s Risk for Use in Crime under Circumstances That Suggest Gun Trafficking

While many handguns are used in crime each year in the USA, most are not. We conducted this study to identify factors present at the time of a handgun’s most recent retail sale that were associated with its subsequent use in crime under circumstances suggesting that the handgun had been trafficked—purchased with the intent of diverting it to criminal use. Handguns acquired in multiple-gun purchases were of particular interest. Using data for 180,321 handguns purchased from federally licensed retailers in California in 1996, we studied attributes of the handguns, the retailers selling them, the purchasers, and the sales transactions. Our outcome measure was a handgun’s recovery by a police agency, followed by a gun ownership trace, conducted by the Bureau of Alcohol, Tobacco, Firearms and Explosives, that determined (a) that the recovery had occurred within 3 years of the handgun’s most recent purchase from a licensed retailer and (b) that the person who possessed the gun when it was recovered by police was not its most recent purchaser. Altogether, 722 handguns were recovered and had trace results that met the additional criteria. Handguns acquired in multiple-gun, same-day transactions were more likely to be traced than were single-purchase handguns (odds ratio [OR] 1.33, 95% confidence intervals [CI] 1.08 to 1.63). This was not the case for multiple-purchase handguns defined more broadly as multiple handguns purchased by one individual over any 30-day period as used in “one-gun-a-month” laws. Bivariate regressions indicated increased risk of a handgun being traced when it sold new for $150 or less (OR 4.28, 95% CI 3.59 to 5.11) or had been purchased by a woman (OR 2.02, 95% CI 1.62 to 2.52). Handguns sold by retailers who also had a relatively high proportion (≥2%) of purchases denied because the prospective purchasers were prohibited from owning firearms were more likely to be traced than were those sold by other retailers (OR 4.09, 95% CI 3.39 to 4.94). These findings persisted in multivariate analyses. Our findings suggest specific strategies for intervention to prevent gun violence

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM

Quantum anti-Zeno effect without wave function reduction

We study the measurement-induced enhancement of the spontaneous decay (called quantum anti-Zeno effect) for a two-level subsystem, where measurements are treated as couplings between the excited state and an auxiliary state rather than the von Neumann's wave function reduction. The photon radiated in a fast decay of the atom, from the auxiliary state to the excited state, triggers a quasi-measurement, as opposed to a projection measurement. Our use of the term "quasi-measurement" refers to a "coupling-based measurement". Such frequent quasi-measurements result in an exponential decay of the survival probability of atomic initial state with a photon emission following each quasi-measurement. Our calculations show that the effective decay rate is of the same form as the one based on projection measurements. What is more important, the survival probability of the atomic initial state which is obtained by tracing over all the photon states is equivalent to the survival probability of the atomic initial state with a photon emission following each quasi-measurement to the order under consideration. That is because the contributions from those states with photon number less than the number of quasi-measurements originate from higher-order processes.Comment: 7 pages, 3 figure

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people