The IceCube Realtime Alert System

Following the detection of high-energy astrophysical neutrinos in 2013, their origin is still unknown. Aiming for the identification of an electromagnetic counterpart of a rapidly fading source, we have implemented a realtime analysis framework for the IceCube neutrino observatory. Several analyses selecting neutrinos of astrophysical origin are now operating in realtime at the detector site in Antarctica and are producing alerts to the community to enable rapid follow-up observations. The goal of these observations is to locate the astrophysical objects responsible for these neutrino signals. This paper highlights the infrastructure in place both at the South Pole detector site and at IceCube facilities in the north that have enabled this fast follow-up program to be developed. Additionally, this paper presents the first realtime analyses to be activated within this framework, highlights their sensitivities to astrophysical neutrinos and background event rates, and presents an outlook for future discoveries.Comment: 33 pages, 9 figures, Published in Astroparticle Physic

Patterns of comorbidity in community-dwelling older people hospitalised for fall-related injury: A cluster analysis

<p>Abstract</p> <p>Background</p> <p>Community-dwelling older people aged 65+ years sustain falls frequently; these can result in physical injuries necessitating medical attention including emergency department care and hospitalisation. Certain health conditions and impairments have been shown to contribute independently to the risk of falling or experiencing a fall injury, suggesting that individuals with these conditions or impairments should be the focus of falls prevention. Since older people commonly have multiple conditions/impairments, knowledge about which conditions/impairments coexist in at-risk individuals would be valuable in the implementation of a targeted prevention approach. The objective of this study was therefore to examine the prevalence and patterns of comorbidity in this population group.</p> <p>Methods</p> <p>We analysed hospitalisation data from Victoria, Australia's second most populous state, to estimate the prevalence of comorbidity in patients hospitalised at least once between 2005-6 and 2007-8 for treatment of acute fall-related injuries. In patients with two or more comorbid conditions (multicomorbidity) we used an agglomerative hierarchical clustering method to cluster comorbidity variables and identify constellations of conditions.</p> <p>Results</p> <p>More than one in four patients had at least one comorbid condition and among patients with comorbidity one in three had multicomorbidity (range 2-7). The prevalence of comorbidity varied by gender, age group, ethnicity and injury type; it was also associated with a significant increase in the average cumulative length of stay per patient. The cluster analysis identified five distinct, biologically plausible clusters of comorbidity: cardiopulmonary/metabolic, neurological, sensory, stroke and cancer. The cardiopulmonary/metabolic cluster was the largest cluster among the clusters identified.</p> <p>Conclusions</p> <p>The consequences of comorbidity clustering in terms of falls and/or injury outcomes of hospitalised patients should be investigated by future studies. Our findings have particular relevance for falls prevention strategies, clinical practice and planning of follow-up services for these patients.</p

Methods of estimation of mitral valve regurgitation for the cardiac surgeon

Mitral valve regurgitation is a relatively common and important heart valve lesion in clinical practice and adequate assessment is fundamental to decision on management, repair or replacement. Disease localised to the posterior mitral valve leaflet or focal involvement of the anterior mitral valve leaflet is most amenable to mitral valve repair, whereas patients with extensive involvement of the anterior leaflet or incomplete closure of the valve are more suitable for valve replacement. Echocardiography is the recognized investigation of choice for heart valve disease evaluation and assessment. However, the technique is depended on operator experience and on patient's hemodynamic profile, and may not always give optimal diagnostic views of mitral valve dysfunction. Cardiac catheterization is related to common complications of an interventional procedure and needs a hemodynamic laboratory. Cardiac magnetic resonance (MRI) seems to be a useful tool which gives details about mitral valve anatomy, precise point of valve damage, as well as the quantity of regurgitation. Finally, despite of its higher cost, cardiac MRI using cine images with optimized spatial and temporal resolution can also resolve mitral valve leaflet structural motion, and can reliably estimate the grade of regurgitation

Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype

<p>Abstract</p> <p>Background</p> <p>Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype.</p> <p>Methods</p> <p>Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument.</p> <p>Results</p> <p>Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation <it>P </it>values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets.</p> <p>Conclusions</p> <p>Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.</p

Air pollution and general practitioner access and utilization: a population based study in Sarnia, 'Chemical Valley,' Ontario

<p>Abstract</p> <p>Background</p> <p>Health impacts of poor environmental quality have been identified in studies around the world and in Canada. While many of the studies have identified associations between air pollution and mortality or morbidity, few have focused on the role of health care as a potential moderator of impacts. This study assessed the determinants of health care access and utilization in the context of ambient air pollution in Sarnia, Ontario, Canada.</p> <p>Methods</p> <p>Residents of Sarnia participated in a Community Health Study administered by phone, while several ambient air pollutants including nitrogen dioxide (NO₂), sulphur dioxide (SO₂) and the volatile organic compounds benzene, toluene, ethylbenzene, mp- and o-xylene (BTEX) were monitored across the city. Land Use Regression models were used to estimate individual exposures to the measured pollutants and logistic regression models were utilized to assess the relative influence of environmental, socioeconomic and health related covariates on general practitioner access and utilization outcomes.</p> <p>Results</p> <p>The results show that general practitioner use increased with levels of exposure to nitrogen dioxide (NO₂- Odds Ratio [OR]: 1.16, <it>p </it>< 0.05) and sulphur dioxide (SO₂- OR: 1.61, <it>p </it>< 0.05). Low household income was a stronger predictor of having no family doctor in areas exposed to high concentrations of NO₂and SO₂. Respondents without regular care living in high pollution areas were also more likely to report travelling or waiting for care in excess of 20 minutes (OR: 3.28, <it>p </it>< 0.05) than their low exposure counterparts (OR: 1.11, <it>p </it>> 0.05).</p> <p>Conclusions</p> <p>This study provides evidence for inequitable health care access and utilization in Sarnia, with particular relevance to its situation as a sentinel high exposure environment. Levels of exposure to pollution appears to influence utilization of health care services, but poor access to primary health care services additionally burden certain groups in Sarnia, Ontario, Canada.</p

Integrin αvβ5 is a primary receptor for adenovirus in CAR-negative cells

<p>Abstract</p> <p>Background</p> <p>Viruses bind to specific cellular receptors in order to infect their hosts. The specific receptors a virus uses are important factors in determining host range, cellular tropism, and pathogenesis. For adenovirus, the existing model of entry requires two receptor interactions. First, the viral fiber protein binds Coxsackie and Adenovirus Receptor (CAR), its primary cellular receptor, which docks the virus to the cell surface. Next, viral penton base engages cellular integrins, coreceptors thought to be required exclusively for internalization and not contributing to binding. However, a number of studies reporting data which conflicts with this simple model have been published. These observations have led us to question the proposed two-step model for adenovirus infection.</p> <p>Results</p> <p>In this study we report that cells which express little to no CAR can be efficiently transduced by adenovirus. Using competition experiments between whole virus and soluble viral fiber protein or integrin blocking peptides, we show virus binding is not dependent on fiber binding to cells but rather on penton base binding cellular integrins. Further, we find that binding to low CAR expressing cells is inhibited specifically by a blocking antibody to integrin αvβ5, demonstrating that in these cells integrin αvβ5 and not CAR is required for adenovirus attachment. The binding mediated by integrin αvβ5 is extremely high affinity, in the picomolar range.</p> <p>Conclusions</p> <p>Our data further challenges the model of adenovirus infection in which binding to primary receptor CAR is required in order for subsequent interactions between adenovirus and integrins to initiate viral entry. In low CAR cells, binding occurs through integrin αvβ5, a receptor previously thought to be used exclusively in internalization. We show for the first time that integrin αvβ5 can be used as an alternate binding receptor.</p

Methods for the guideline-based development of quality indicators--a systematic review

<p>Abstract</p> <p>Background</p> <p>Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.</p> <p>Methods</p> <p>We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.</p> <p>Results</p> <p>From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.</p> <p>Conclusions</p> <p>Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.</p

Protein 3D Structure Computed from Evolutionary Sequence Variation

The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing

Diverse and Active Roles for Adipocytes During Mammary Gland Growth and Function

The mammary gland is unique in its requirement to develop in close association with a depot of adipose tissue that is commonly referred to as the mammary fat pad. As discussed throughout this issue, the mammary fat pad represents a complex stromal microenvironment that includes a variety of cell types. In this article we focus on adipocytes as local regulators of epithelial cell growth and their function during lactation. Several important considerations arise from such a discussion. There is a clear and close interrelationship between different stromal tissue types within the mammary fat pad and its adipocytes. Furthermore, these relationships are both stage- and species-dependent, although many questions remain unanswered regarding their roles in these different states. Several lines of evidence also suggest that adipocytes within the mammary fat pad may function differently from those in other fat depots. Finally, past and future technologies present a variety of opportunities to model these complexities in order to more precisely delineate the many potential functions of adipocytes within the mammary glands. A thorough understanding of the role for this cell type in the mammary glands could present numerous opportunities to modify both breast cancer risk and lactation performance