Building Data-Driven Pathways From Routinely Collected Hospital Data:A Case Study on Prostate Cancer

Background: Routinely collected data in hospitals is complex, typically heterogeneous, and scattered across multiple Hospital Information Systems (HIS). This big data, created as a byproduct of health care activities, has the potential to provide a better understanding of diseases, unearth hidden patterns, and improve services and cost. The extent and uses of such data rely on its quality, which is not consistently checked, nor fully understood. Nevertheless, using routine data for the construction of data-driven clinical pathways, describing processes and trends, is a key topic receiving increasing attention in the literature. Traditional algorithms do not cope well with unstructured processes or data, and do not produce clinically meaningful visualizations. Supporting systems that provide additional information, context, and quality assurance inspection are needed. Objective: The objective of the study is to explore how routine hospital data can be used to develop data-driven pathways that describe the journeys that patients take through care, and their potential uses in biomedical research; it proposes a framework for the construction, quality assessment, and visualization of patient pathways for clinical studies and decision support using a case study on prostate cancer. Methods: Data pertaining to prostate cancer patients were extracted from a large UK hospital from eight different HIS, validated, and complemented with information from the local cancer registry. Data-driven pathways were built for each of the 1904 patients and an expert knowledge base, containing rules on the prostate cancer biomarker, was used to assess the completeness and utility of the pathways for a specific clinical study. Software components were built to provide meaningful visualizations for the constructed pathways. Results: The proposed framework and pathway formalism enable the summarization, visualization, and querying of complex patient-centric clinical information, as well as the computation of quality indicators and dimensions. A novel graphical representation of the pathways allows the synthesis of such information. Conclusions: Clinical pathways built from routinely collected hospital data can unearth information about patients and diseases that may otherwise be unavailable or overlooked in hospitals. Data-driven clinical pathways allow for heterogeneous data (ie, semistructured and unstructured data) to be collated over a unified data model and for data quality dimensions to be assessed. This work has enabled further research on prostate cancer and its biomarkers, and on the development and application of methods to mine, compare, analyze, and visualize pathways constructed from routine data. This is an important development for the reuse of big data in hospitals

Munchausen by internet: current research and future directions.

The Internet has revolutionized the health world, enabling self-diagnosis and online support to take place irrespective of time or location. Alongside the positive aspects for an individual's health from making use of the Internet, debate has intensified on how the increasing use of Web technology might have a negative impact on patients, caregivers, and practitioners. One such negative health-related behavior is Munchausen by Internet

The failure of suicide prevention in primary care: family and GP perspectives - a qualitative study

Background Although Primary care is crucial for suicide prevention, clinicians tend to report completed suicides in their care as non-preventable. We aimed to examine systemic inadequacies in suicide prevention from the perspectives of bereaved family members and GPs.Methods Qualitative study of 72 relatives or close friends bereaved by suicide and 19 General Practitioners who have experienced the suicide of patients.Results Relatives highlight failures in detecting symptoms and behavioral changes and the inability of GPs to understand the needs of patients and their social contexts. A perceived overreliance on anti-depressant treatment is a major source of criticism by family members. GPs tend to lack confidence in the recognition and management of suicidal patients, and report structural inadequacies in service provision.Conclusions Mental health and primary care services must find innovative and ethical ways to involve families in the decision-making process for patients at risk of suicide

Stable isotope analysis provides new information on winter habitat use of declining avian migrants that is relevant to their conservation

Winter habitat use and the magnitude of migratory connectivity are important parameters when assessing drivers of the marked declines in avian migrants. Such information is unavailable for most species. We use a stable isotope approach to assess these factors for three declining African-Eurasian migrants whose winter ecology is poorly known: wood warbler Phylloscopus sibilatrix, house martin Delichon urbicum and common swift Apus apus. Spatially segregated breeding wood warbler populations (sampled across a 800 km transect), house martins and common swifts (sampled across a 3,500 km transect) exhibited statistically identical intra-specific carbon and nitrogen isotope ratios in winter grown feathers. Such patterns are compatible with a high degree of migratory connectivity, but could arise if species use isotopically similar resources at different locations. Wood warbler carbon isotope ratios are more depleted than typical for African-Eurasian migrants and are compatible with use of moist lowland forest. The very limited variance in these ratios indicates specialisation on isotopically restricted resources, which may drive the similarity in wood warbler populations' stable isotope ratios and increase susceptibility to environmental change within its wintering grounds. House martins were previously considered to primarily use moist montane forest during the winter, but this seems unlikely given the enriched nature of their carbon isotope ratios. House martins use a narrower isotopic range of resources than the common swift, indicative of increased specialisation or a relatively limited wintering range; both factors could increase house martins' vulnerability to environmental change. The marked variance in isotope ratios within each common swift population contributes to the lack of population specific signatures and indicates that the species is less vulnerable to environmental change in sub-Saharan Africa than our other focal species. Our findings demonstrate how stable isotope research can contribute to understanding avian migrants' winter ecology and conservation status

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Photobrightening in Lead Halide Perovskites: Observations, Mechanisms, and Future Potential

There has been a meteoric rise in commercial potential of lead halide perovskite optoelectronic devices since photovoltaic cells (2009) and light emitting diodes (2014) based on these materials were first demonstrated. One key challenge common to each of these optoelectronic devices is the need to suppress non-radiative recombination, a process that limits the maximum achievable efficiency in photovoltaic cells and light emitting diodes. In this Progress Report, we dissect recent studies that seek to minimise this loss pathway in perovskites through a photobrightening effect, whereby the luminescence efficiency is enhanced through a light illumination passivation treatment. We highlight the sensitivity of this effect to experimental considerations such as atmosphere, photon energy, photon dose, and also the role of perovskite composition and morphology; under certain conditions there can even be photodarkening effects. Consideration of these factors is critical to resolve seemingly conflicting literature reports. We scrutinise proposed mechanisms, concluding that there is some consensus but further work is needed to identify the specific defects being passivated and elucidate universal mechanisms. Finally, we discuss the prospects for these treatments to minimise halide migration and push the properties of polycrystalline films towards those of their single-crystal counterparts

Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages

There is increasing evidence that strain variation in Mycobacterium tuberculosis complex (MTBC) might influence the outcome of tuberculosis infection and disease. To assess genotype-phenotype associations, phylogenetically robust molecular markers and appropriate genotyping tools are required. Most current genotyping methods for MTBC are based on mobile or repetitive DNA elements. Because these elements are prone to convergent evolution, the corresponding genotyping techniques are suboptimal for phylogenetic studies and strain classification. By contrast, single nucleotide polymorphisms (SNP) are ideal markers for classifying MTBC into phylogenetic lineages, as they exhibit very low degrees of homoplasy. In this study, we developed two complementary SNP-based genotyping methods to classify strains into the six main human-associated lineages of MTBC, the 'Beijing' sublineage, and the clade comprising Mycobacterium bovis and Mycobacterium caprae. Phylogenetically informative SNPs were obtained from 22 MTBC whole-genome sequences. The first assay, referred to as MOL-PCR, is a ligation-dependent PCR with signal detection by fluorescent microspheres and a Luminex flow cytometer, which simultaneously interrogates eight SNPs. The second assay is based on six individual TaqMan real-time PCR assays for singleplex SNP-typing. We compared MOL-PCR and TaqMan results in two panels of clinical MTBC isolates. Both methods agreed fully when assigning 36 well-characterized strains into the main phylogenetic lineages. The sensitivity in allele-calling was 98.6% and 98.8% for MOL-PCR and TaqMan, respectively. Typing of an additional panel of 78 unknown clinical isolates revealed 99.2% and 100% sensitivity in allele-calling, respectively, and 100% agreement in lineage assignment between both methods. While MOL-PCR and TaqMan are both highly sensitive and specific, MOL-PCR is ideal for classification of isolates with no previous information, whereas TaqMan is faster for confirmation. Furthermore, both methods are rapid, flexible and comparably inexpensive