Comparison of Statistical Algorithms for the Detection of Infectious Disease Outbreaks in Large Multiple Surveillance Systems

A large-scale multiple surveillance system for infectious disease outbreaks has been in operation in England and Wales since the early 1990s. Changes to the statistical algorithm at the heart of the system were proposed and the purpose of this paper is to compare two new algorithms with the original algorithm. Test data to evaluate performance are created from weekly counts of the number of cases of each of more than 2000 diseases over a twenty-year period. The time series of each disease is separated into one series giving the baseline (background) disease incidence and a second series giving disease outbreaks. One series is shifted forward by twelve months and the two are then recombined, giving a realistic series in which it is known where outbreaks have been added. The metrics used to evaluate performance include a scoring rule that appropriately balances sensitivity against specificity and is sensitive to variation in probabilities near 1. In the context of disease surveillance, a scoring rule can be adapted to reflect the size of outbreaks and this was done. Results indicate that the two new algorithms are comparable to each other and better than the algorithm they were designed to replace

Variation in hospital cleaning practice and process in Australian hospitals: A structured mapping exercise

Background The purpose of this paper is to highlight the range of cleaning practices and processes in 11 Australian hospitals and to discuss the challenges this variation poses to the implementation of clinical trials or changes to hospital cleaning practices. Methods A cross-sectional study design was used to determine cleaning practices and processes in hospitals participating in the ‘Researching Effective Approaches to Cleaning in Hospitals’ (REACH) study. A standardised template and approach was used to collect information. Data collection activities included structured on-site discussions, a review of hospital practices and a document review of policy and procedural documents related to cleaning. Results Variations in the auditing process used to evaluate environmental cleanliness, cleaning practices, product use, training and communication pathways available to cleaning staff were identified. There was also variation in workforce structure and responsibilities for cleaning. Conclusion This paper is the first to describe the differences in cleaning practices between Australian hospitals. The variations identified present a number of challenges for the conduct of research and have important implications for both monitoring of and standards for cleanliness. These challenges include implementing a practice change or cleaning study where hospitals have different processes, practices and structures

Statin Induced Myopathy and Myalgia: Time Trend Analysis and Comparison of Risk Associated with Statin Class from 1991–2006

BACKGROUND: Statins are widely used as a cholesterol lowering medication, reduce cardiovascular mortality and morbidity in high risk patients; and only rarely cause serious adverse drug reactions (ADRs). UK primary care databases of morbidity and prescription data, which now cover several million people, have potential for more powerful analytical approaches to study ADRs including adjusting for confounders and examining temporal effects. METHODS: Case-crossover design in detecting statin associated myopathy ADR in 93, 831 patients, using two independent primary care databases (1991-2006). We analysed risk by drug class, by disease code and cumulative year, exploring different cut-off exposure times and confounding by temporality. RESULTS: Using a 12 and 26 week exposure period, large risk ratios (RR) are associated with all classes of statins and fibrates for myopathy: RR 10.6 (9.8-11.4) and 19.9 (17.6-22.6) respectively. At 26 weeks, the largest risks are with fluvastatin RR 33.3 (95% CI 16.8-66.0) and ciprofibrate (with previous statin use) RR 40.5 (95% CI 13.4-122.0). AT 12 weeks the differences between cerivastatin and atorvastatin RR for myopathy were found to be significant, RR 2.05 (95% CI 1.2-3.5), and for rosuvastatin and fluvastatin RR 3.0 (95% CI 1.6-5.7). After 12 months of statin initiation, the relative risk for myopathy for all statins and fibrates increased to 25.7 (95% CI 21.8-30.3). Furthermore, this signal was detected within 2 years of first events being recorded. Our data suggests an annual incidence of statin induced myopathy or myalgia of around 11.4 for 16, 591 patients or 689 per million per year. CONCLUSION: There may be differential risks associated with some classes of statin and fibrate. Myopathy related to statin or fibrate use may persist after a long exposure time (12 months or more). These methods could be applied for early detection of harmful drug side effects, using similar primary care diagnostic and prescribing data

Beyond crime statistics: the construction and application of a criminogenity monitor in Amsterdam

Criminologists have devoted a great deal of attention to risk factors - also called criminogenic factors - leading to criminal offending. This paper presents a criminogenity monitor which includes 19 risk factors that underlie crime. These factors do not themselves cause criminal behaviour; rather, they must be seen as signals that crimes may be committed. After discussing how the criminogenity monitor was constructed, we apply the risk factors we examined to the situation in Amsterdam, capital city of the Netherlands. The monitor is intended to function particularly as an instrument to rationalise policy-makers' work in targeting and preventing symptoms of crime at three geographical levels: the entire city, its boroughs and its neighbourhoods. © 2012 The Author(s)

The effectiveness of Chance UK's mentoring programme in improving behavioural and emotional outcomes in primary school children with behavioural difficulties: study protocol for a randomised controlled trial

BACKGROUND: There is a need to build the evidence base of early interventions to promote children's health and development in the UK. Chance UK is a voluntary sector organisation based in London that delivers a 12-month mentoring programme for primary school children identified by teachers and parents as having behavioural and emotional difficulties. The aim of the study is to determine the effectiveness of the programme in terms of children's behaviour and emotional well-being; this is the primary outcome of the trial. METHODS/DESIGN: A randomised controlled trial will be conducted in which participants are randomly allocated on a dynamic basis to one of two possible arms: the intervention arm (n = 123) will be offered the mentoring programme, and the control arm (n = 123) will be offered services as usual. Outcome data will be collected at three points: pre-intervention (baseline), mid-way through the mentoring year (c.9 months after randomisation) and post- mentoring programme (c.16 months after randomisation). DISCUSSION: This study will further enhance the evidence for early intervention mentoring programmes for child behaviour and emotional well-being in the UK. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47154925 . Retrospectively registered 9 September 2014

Internal deformation of the subducted Nazca slab inferred from seismic anisotropy

Within oceanic lithosphere a fossilized fabric is often preserved originating from the time of plate formation. Such fabric is thought to form at the mid-ocean ridge when olivine crystals align with the direction of plate spreading1, 2. It is unclear, however, whether this fossil fabric is preserved within slabs during subduction or overprinted by subduction-induced deformation. The alignment of olivine crystals, such as within fossil fabrics, can generate anisotropy that is sensed by passing seismic waves. Seismic anisotropy is therefore a useful tool for investigating the dynamics of subduction zones, but it has so far proved difficult to observe the anisotropic properties of the subducted slab itself. Here we analyse seismic anisotropy in the subducted Nazca slab beneath Peru and find that the fast direction of seismic wave propagation aligns with the contours of the slab. We use numerical modelling to simulate the olivine fabric created at the mid-ocean ridge, but find it is inconsistent with our observations of seismic anisotropy in the subducted Nazca slab. Instead we find that an orientation of the olivine crystal fast axes aligned parallel to the strike of the slab provides the best fit, consistent with along-strike extension induced by flattening of the slab during subduction (A. Kumar et al., manuscript in preparation). We conclude that the fossil fabric has been overprinted during subduction and that the Nazca slab must therefore be sufficiently weak to undergo internal deformation

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

Individual, family and offence characteristics of high risk childhood offenders: comparing non-offending, one-time offending and re-offending Dutch-Moroccan migrant children in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Childhood offenders are at an increased risk for developing mental health, social and educational problems later in life. An early onset of offending is a strong predictor for future persistent offending. Childhood offenders from ethnic minority groups are a vulnerable at-risk group. However, up until now, no studies have focused on them.</p> <p>Aims</p> <p>To investigate which risk factors are associated with (re-)offending of childhood offenders from an ethnic minority.</p> <p>Method</p> <p>Dutch-Moroccan boys, who were registered by the police in the year 2006-2007, and their parents as well as a control group (n = 40) were interviewed regarding their individual and family characteristics. Two years later a follow-up analysis of police data was conducted to identify one-time offenders (n = 65) and re-offenders (n = 35).</p> <p>Results</p> <p>All groups, including the controls, showed substantial problems. Single parenthood (OR 6.0) and financial problems (OR 3.9) distinguished one-time offenders from controls. Reading problems (OR 3.8), having an older brother (OR 5.5) and a parent having Dutch friends (OR 4.3) distinguished re-offenders from one-time offenders. First offence characteristics were not predictive for re-offending. The control group reported high levels of emotional problems (33.3%). Parents reported not needing help for their children but half of the re-offender's families were known to the Child Welfare Agency, mostly in a juridical framework.</p> <p>Conclusion</p> <p>The Moroccan subgroup of childhood offenders has substantial problems that might hamper healthy development. Interventions should focus on reaching these families tailored to their needs and expectations using a multi-system approach.</p