Simplifying the interpretation of continuous time models for spatio-temporal networks

Autoregressive and moving average models for temporally dynamic networks treat time as a series of discrete steps which assumes even intervals between data measurements and can introduce bias if this assumption is not met. Using real and simulated data from the London Underground network, this paper illustrates the use of continuous time multilevel models to capture temporal trajectories of edge properties without the need for simultaneous measurements, along with two methods for producing interpretable summaries of model results. These including extracting ‘features’ of temporal patterns (e.g. maxima, time of maxima) which have utility in understanding the network properties of each connection and summarising whole-network properties as a continuous function of time which allows estimation of network properties at any time without temporal aggregation of non-simultaneous measurements. Results for temporal pattern features in the response variable were captured with reasonable accuracy. Variation in the temporal pattern features for the exposure variable was underestimated by the models. The models showed some lack of precision. Both model summaries provided clear ‘real-world’ interpretations and could be applied to data from a range of spatio-temporal network structures (e.g. rivers, social networks). These models should be tested more extensively in a range of scenarios, with potential improvements such as random effects in the exposure variable dimension

Saccharomyces cerevisiae mutants affected in vacuole assembly or vacuolar H+-ATPase are hypersensitive to lead (Pb) toxicity

Lead is an important environmental pollutant. The role of vacuole, in Pb detoxification, was studied using a vacuolar protein sorting mutant strain (vps16Δ), belonging to class C mutants. Cells disrupted in VPS16 gene, did not display a detectable vacuolar-like structure. Based on the loss of cell proliferation capacity, it was found that cells from vps16Δ mutant exhibited a hypersensitivity to Pb-induced toxicity, compared to wild type (WT) strain. The function of vacuolar H+-ATPase (V-ATPase), in Pb detoxification, was evaluated using mutants with structurally normal vacuoles but defective in subunits of catalytic (vma1Δ or vma2Δ) or membrane domain (vph1Δ or vma3Δ) of V-ATPase. All mutants tested, lacking a functional V-ATPase, displayed an increased susceptibility to Pb, comparatively to cells from WT strain. Modification of vacuolar morphology, in Pb-exposed cells, was visualized using a Vma2p-GFP strain. The treatment of yeast cells with Pb originated the fusion of the medium size vacuolar lobes into one enlarged vacuole. In conclusion, it was found that vacuole plays an important role in the detoxification of Pb in Saccharomyces cerevisiae; in addition, a functional V-ATPase was required for Pb compartmentalization.The authors thank the Fundacao para a Ciencia e a Tecnologia (FCT) through the Portuguese Government for their financial support of this work through the grant PEST-OE/EQB/LA0023/2011 to IBB

Adjuvant radiation therapy in metastatic lymph nodes from melanoma

<p>Abstract</p> <p>Purpose</p> <p>To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma.</p> <p>Patients and methods</p> <p>86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy.</p> <p>Results</p> <p>The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004).</p> <p>Conclusion</p> <p>Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension).</p

Adjustment for time-invariant and time-varying confounders in ‘unexplained residuals’ models for longitudinal data within a causal framework and associated challenges

‘Unexplained residuals’ models have been used within lifecourse epidemiology to model an exposure measured longitudinally at several time points in relation to a distal outcome. It has been claimed that these models have several advantages, including: the ability to estimate multiple total causal effects in a single model, and additional insight into the effect on the outcome of greater-than-expected increases in the exposure compared to traditional regression methods. We evaluate these properties and prove mathematically how adjustment for confounding variables must be made within this modelling framework. Importantly, we explicitly place unexplained residual models in a causal framework using directed acyclic graphs. This allows for theoretical justification of appropriate confounder adjustment and provides a framework for extending our results to more complex scenarios than those examined in this paper. We also discuss several interpretational issues relating to unexplained residual models within a causal framework. We argue that unexplained residual models offer no additional insights compared to traditional regression methods, and, in fact, are more challenging to implement; moreover, they artificially reduce estimated standard errors. Consequently, we conclude that unexplained residual models, if used, must be implemented with great care

Comparison of user groups' perspectives of barriers and facilitators to implementing electronic health records: a systematic review

<p>Abstract</p> <p>Background</p> <p>Electronic health record (EHR) implementation is currently underway in Canada, as in many other countries. These ambitious projects involve many stakeholders with unique perceptions of the implementation process. EHR users have an important role to play as they must integrate the EHR system into their work environments and use it in their everyday activities. Users hold valuable, first-hand knowledge of what can limit or contribute to the success of EHR implementation projects. A comprehensive synthesis of EHR users' perceptions is key to successful future implementation. This systematic literature review was aimed to synthesize current knowledge of the barriers and facilitators influencing shared EHR implementation among its various users.</p> <p>Methods</p> <p>Covering a period from 1999 to 2009, a literature search was conducted on nine electronic databases. Studies were included if they reported on users' perceived barriers and facilitators to shared EHR implementation, in healthcare settings comparable to Canada. Studies in all languages with an empirical study design were included. Quality and relevance of the studies were assessed. Four EHR user groups were targeted: physicians, other health care professionals, managers, and patients/public. Content analysis was performed independently by two authors using a validated extraction grid with pre-established categorization of barriers and facilitators for each group of EHR users.</p> <p>Results</p> <p>Of a total of 5,695 potentially relevant publications identified, 117 full text publications were obtained after screening titles and abstracts. After review of the full articles, 60 publications, corresponding to 52 studies, met the inclusion criteria. The most frequent adoption factors common to all user groups were design and technical concerns, ease of use, interoperability, privacy and security, costs, productivity, familiarity and ability with EHR, motivation to use EHR, patient and health professional interaction, and lack of time and workload. Each user group also identified factors specific to their professional and individual priorities.</p> <p>Conclusions</p> <p>This systematic review presents innovative research on the barriers and facilitators to EHR implementation. While important similarities between user groups are highlighted, differences between them demonstrate that each user group also has a unique perspective of the implementation process that should be taken into account.</p