Search for Lorentz Violation in km(3)-Scale Neutrino Telescopes

Presented at the Seventh Meeting on CPT and Lorentz Symmetry, Bloomington, Indiana, June 20-24, 2016Presented at the Seventh Meeting on CPT and Lorentz Symmetry, Bloomington, Indiana, June 20-24, 2016G.C., C.A., and J.C. are supported by NSF grants 1505858 and 1505855. T.K. is supported by the Science and Technology Facilities Council, UK. A.K. was supported in part by the NSF under grants 0937462 and 1306958 and by the University of Wisconsin Research Committee

High g-Force Rollercoaster Rides Induce Sinus Tachycardia but No Cardiac Arrhythmias in Healthy Children

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Theme park operators and medical professionals advise children with heart conditions against using rollercoaster rides, but these recommendations are not evidence-based. The underlying assumption is that the combination of adrenergic stimulation through stress and acceleration might trigger arrhythmias in susceptible individuals. We conducted a cross-sectional observational study to assess heart rate and rhythm in healthy children during commercial rollercoaster rides. Twenty healthy children (9 male) aged 11-15 (mean 13.3 ± 1.4) years underwent continuous heart rate and rhythm monitoring (2-lead ECG) from 5 min before until 10 min after each of 4 high speed (>50 km h(-1)), high g-force (>4) commercial rollercoaster rides. Total recording time was 13 h 20 min. No arrhythmic events were detected. Resting heart rate was 81 ± 10 b min(-1) and increased to 158 ± 20 b·min(-1) during rides. The highest mean HR (165 ± 23 b min(-1)) was observed on the ride with the lowest g-force (4.5 g), but one of the highest speeds (100 km h(-1)). Anticipatory tachycardia (126 ± 15 b min(-1)) within 5 min was frequently observed. A 10 min recovery HR (124 ± 17 b min(-1)) was 56 % greater than resting HR. The speed and g-force experienced on roller coasters induce sinus tachycardia but do not elicit pathological arrhythmias in healthy children.This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Unit in Cardiovascular Disease at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. Dr Pieles is the holder of an NIHR Academic Clinical Lectureship in Paediatric Cardiology. We would like to thank Novacor Ltd (Swanley, Kent, UK) for providing portable ECG monitoring equipment and Thorpe Park (Merlin Entertainments PLC, Poole, Dorset, UK) for their support during data acquisition. We thank all of the children and their families for participating in this study

Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology

“It’s hard to tell”. The challenges of scoring patients on standardised outcome measures by multidisciplinary teams: a case study of Neurorehabilitation

Background Interest is increasing in the application of standardised outcome measures in clinical practice. Measures designed for use in research may not be sufficiently precise to be used in monitoring individual patients. However, little is known about how clinicians and in particular, multidisciplinary teams, score patients using these measures. This paper explores the challenges faced by multidisciplinary teams in allocating scores on standardised outcome measures in clinical practice. Methods Qualitative case study of an inpatient neurorehabilitation team who routinely collected standardised outcome measures on their patients. Data were collected using non participant observation, fieldnotes and tape recordings of 16 multidisciplinary team meetings during which the measures were recited and scored. Eleven clinicians from a range of different professions were also interviewed. Data were analysed used grounded theory techniques. Results We identified a number of instances where scoring the patient was 'problematic'. In 'problematic' scoring, the scores were uncertain and subject to revision and adjustment. They sometimes required negotiation to agree on a shared understanding of concepts to be measured and the guidelines for scoring. Several factors gave rise to this problematic scoring. Team members' knowledge about patients' problems changed over time so that initial scores had to be revised or dismissed, creating an impression of deterioration when none had occurred. Patients had complex problems which could not easily be distinguished from each other and patients themselves varied in their ability to perform tasks over time and across different settings. Team members from different professions worked with patients in different ways and had different perspectives on patients' problems. This was particularly an issue in the scoring of concepts such as anxiety, depression, orientation, social integration and cognitive problems. Conclusion From a psychometric perspective these problems would raise questions about the validity, reliability and responsiveness of the scores. However, from a clinical perspective, such characteristics are an inherent part of clinical judgement and reasoning. It is important to highlight the challenges faced by multidisciplinary teams in scoring patients on standardised outcome measures but it would be unwarranted to conclude that such challenges imply that these measures should not be used in clinical practice for decision making about individual patients. However, our findings do raise some concerns about the use of such measures for performance management

Why is it difficult to implement e-health initiatives? A qualitative study

<b>Background</b> The use of information and communication technologies in healthcare is seen as essential for high quality and cost-effective healthcare. However, implementation of e-health initiatives has often been problematic, with many failing to demonstrate predicted benefits. This study aimed to explore and understand the experiences of implementers - the senior managers and other staff charged with implementing e-health initiatives and their assessment of factors which promote or inhibit the successful implementation, embedding, and integration of e-health initiatives.<p></p> <b>Methods</b> We used a case study methodology, using semi-structured interviews with implementers for data collection. Case studies were selected to provide a range of healthcare contexts (primary, secondary, community care), e-health initiatives, and degrees of normalization. The initiatives studied were Picture Archiving and Communication System (PACS) in secondary care, a Community Nurse Information System (CNIS) in community care, and Choose and Book (C&B) across the primary-secondary care interface. Implementers were selected to provide a range of seniority, including chief executive officers, middle managers, and staff with 'on the ground' experience. Interview data were analyzed using a framework derived from Normalization Process Theory (NPT).<p></p> <b>Results</b> Twenty-three interviews were completed across the three case studies. There were wide differences in experiences of implementation and embedding across these case studies; these differences were well explained by collective action components of NPT. New technology was most likely to 'normalize' where implementers perceived that it had a positive impact on interactions between professionals and patients and between different professional groups, and fit well with the organisational goals and skill sets of existing staff. However, where implementers perceived problems in one or more of these areas, they also perceived a lower level of normalization.<p></p> <b>Conclusions</b> Implementers had rich understandings of barriers and facilitators to successful implementation of e-health initiatives, and their views should continue to be sought in future research. NPT can be used to explain observed variations in implementation processes, and may be useful in drawing planners' attention to potential problems with a view to addressing them during implementation planning

Effects of Green Tea Catechins and Theanine on Preventing Influenza Infection among Healthcare Workers: A Randomized Controlled Trial

<p>Abstract</p> <p>Background</p> <p>Experimental studies have revealed that green tea catechins and theanine prevent influenza infection, while the clinical evidence has been inconclusive. This study was conducted to determine whether taking green tea catechins and theanine can clinically prevent influenza infection.</p> <p>Methods</p> <p><b>Design, Setting, and Participants</b>: A randomized, double-blind, placebo-controlled trial of 200 healthcare workers conducted for 5 months from November 9, 2009 to April 8, 2010 in three healthcare facilities for the elderly in Higashimurayama, Japan.</p> <p><b>Interventions</b>: The catechin/theanine group received capsules including green tea catechins (378 mg/day) and theanine (210 mg/day). The control group received placebo.</p> <p><b>Main Outcome Measures</b>: The primary outcome was the incidence of clinically defined influenza infection. Secondary outcomes were (1) laboratory-confirmed influenza with viral antigen measured by immunochromatographic assay and (2) the time for which the patient was free from clinically defined influenza infection, i.e., the period between the start of intervention and the first diagnosis of influenza infection, based on clinically defined influenza infection.</p> <p>Results</p> <p>Eligible healthcare workers (n = 197) were enrolled and randomly assigned to an intervention; 98 were allocated to receive catechin/theanine capsules and 99 to placebo. The incidence of clinically defined influenza infection was significantly lower in the catechin/theanine group (4 participants; 4.1%) compared with the placebo group (13 participants; 13.1%) (adjusted OR, 0.25; 95% CI, 0.07 to 0.76, <it>P </it>= 0.022). The incidence of laboratory-confirmed influenza infection was also lower in the catechin/theanine group (1 participant; 1.0%) than in the placebo group (5 participants; 5.1%), but this difference was not significant (adjusted OR, 0.17; 95% CI, 0.01 to 1.10; <it>P </it>= 0.112). The time for which the patient was free from clinically defined influenza infection was significantly different between the two groups (adjusted HR, 0.27; 95% CI, 0.09 to 0.84; <it>P </it>= 0.023).</p> <p>Conclusions</p> <p>Among healthcare workers for the elderly, taking green tea catechins and theanine may be effective prophylaxis for influenza infection.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01008020">NCT01008020</a></p

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Diversity of Color Vision: Not All Australian Marsupials Are Trichromatic

Color vision in marsupials has recently emerged as a particularly interesting case among mammals. It appears that there are both dichromats and trichromats among closely related species. In contrast to primates, marsupials seem to have evolved a different type of trichromacy that is not linked to the X-chromosome. Based on microspectrophotometry and retinal whole-mount immunohistochemistry, four trichromatic marsupial species have been described: quokka, quenda, honey possum, and fat-tailed dunnart. It has, however, been impossible to identify the photopigment of the third cone type, and genetically, all evidence so far suggests that all marsupials are dichromatic. The tammar wallaby is the only Australian marsupial to date for which there is no evidence of a third cone type. To clarify whether the wallaby is indeed a dichromat or trichromatic like other Australian marsupials, we analyzed the number of cone types in the “dichromatic” wallaby and the “trichromatic” dunnart. Employing identical immunohistochemical protocols, we confirmed that the wallaby has only two cone types, whereas 20–25% of cones remained unlabeled by S- and LM-opsin antibodies in the dunnart retina. In addition, we found no evidence to support the hypothesis that the rod photopigment (rod opsin) is expressed in cones which would have explained the absence of a third cone opsin gene. Our study is the first comprehensive and quantitative account of color vision in Australian marsupials where we now know that an unexpected diversity of different color vision systems appears to have evolved

Pattern of the Divergence of Olfactory Receptor Genes during Tetrapod Evolution

The olfactory receptor (OR) multigene family is responsible for the sense of smell in vertebrate species. OR genes are scattered widely in our chromosomes and constitute one of the largest gene families in eutherian genomes. Some previous studies revealed that eutherian OR genes diverged mainly during early mammalian evolution. However, the exact period when, and the ecological reason why eutherian ORs strongly diverged has remained unclear. In this study, I performed a strict data mining effort for marsupial opossum OR sequences and bootstrap analyses to estimate the periods of chromosomal migrations and gene duplications of OR genes during tetrapod evolution. The results indicate that chromosomal migrations occurred mainly during early vertebrate evolution before the monotreme-placental split, and that gene duplications occurred mainly during early mammalian evolution between the bird-mammal split and marsupial-placental split, coinciding with the reduction of opsin genes in primitive mammals. It could be thought that the previous chromosomal dispersal allowed the OR genes to subsequently expand easily, and the nocturnal adaptation of early mammals might have triggered the OR gene expansion