Comparison of cytokine and phosphoprotein profiles in idiopathic and Crohn's disease-related perianal fistula.

BACKGROUND: Perianal fistulae are either primary (idiopathic) or secondary [commonly associated with Crohn's disease, (CD)]. It is assumed, although not proven, that the pathophysiology differs. AIM: To systematically compare the clinical phenotypes, cytokine and phosphoprotein profiles of idiopathic and CD-related perianal fistulae. METHODS: Sixty-one patients undergoing surgery for perianal fistula were prospectively recruited (48 idiopathic, 13 CD) into a cohort study. Clinical data, including the Perineal Disease Activity Index (PDAI) and EQ-5D-5L were collected. Biopsies of the fistula tract, granulation tissue, internal opening mucosa and rectal mucosa were obtained at surgery. Concentrations of 30 cytokines and 39 phosphoproteins were measured in each biopsy using a magnetic bead multiplexing instrument and a chemiluminescent antibody array respectively. Over 12000 clinical and 23500 laboratory measurements were made. RESULTS: The PDAI was significantly higher (indicating more active disease) in the CD group with a mean difference of 2.40 (95%CI: 0.52-4.28, P = 0.01). Complex pathoanatomy was more prevalent in the CD group, namely more multiple fistulae, supralevator extensions, collections and rectal thickening. The IL-12p70 concentration at the internal opening specimen site was significantly higher (median difference 19.7 pg/mL, 99%CI: 0.2-40.4, P = 0.008) and the IL-1RA/IL-1β ratio was significantly lower in the CD group at the internal opening specimen site (median difference 15.0, 99%CI = 0.4-50.5, P = 0.008). However in the remaining 27 cytokines and all 39 of the phosphoproteins across the four biopsy sites, no significant differences were found between the groups. CONCLUSION: CD-related perianal fistulae are more clinically severe and anatomically complex than idiopathic perianal fistulae. However, overall there are no major differences in cytokine and phosphoprotein profiles

Photonic Analogue of Two-dimensional Topological Insulators and Helical One-Way Edge Transport in Bi-Anisotropic Metamaterials

Recent progress in understanding the topological properties of condensed matter has led to the discovery of time-reversal invariant topological insulators. Because of limitations imposed by nature, topologically non-trivial electronic order seems to be uncommon except in small-band-gap semiconductors with strong spin-orbit interactions. In this Article we show that artificial electromagnetic structures, known as metamaterials, provide an attractive platform for designing photonic analogues of topological insulators. We demonstrate that a judicious choice of the metamaterial parameters can create photonic phases that support a pair of helical edge states, and that these edge states enable one-way photonic transport that is robust against disorder.Comment: 13 pages, 3 figure

Speaking and Listening with the Eyes: Gaze Signaling during Dyadic Interactions

Cognitive scientists have long been interested in the role that eye gaze plays in social interactions. Previous research suggests that gaze acts as a signaling mechanism and can be used to control turn-taking behaviour. However, early research on this topic employed methods of analysis that aggregated gaze information across an entire trial (or trials), which masks any temporal dynamics that may exist in social interactions. More recently, attempts have been made to understand the temporal characteristics of social gaze but little research has been conducted in a natural setting with two interacting participants. The present study combines a temporally sensitive analysis technique with modern eye tracking technology to 1) validate the overall results from earlier aggregated analyses and 2) provide insight into the specific moment-to-moment temporal characteristics of turn-taking behaviour in a natural setting. Dyads played two social guessing games (20 Questions and Heads Up) while their eyes were tracked. Our general results are in line with past aggregated data, and using cross-correlational analysis on the specific gaze and speech signals of both participants we found that 1) speakers end their turn with direct gaze at the listener and 2) the listener in turn begins to speak with averted gaze. Convergent with theoretical models of social interaction, our data suggest that eye gaze can be used to signal both the end and the beginning of a speaking turn during a social interaction. The present study offers insight into the temporal dynamics of live dyadic interactions and also provides a new method of analysis for eye gaze data when temporal relationships are of interest

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus

Analyzing the Impacts of Off-Road Vehicle (ORV) Trails on Watershed Processes in Wrangell-St. Elias National Park and Preserve, Alaska

Trails created by off-road vehicles (ORV) in boreal lowlands are known to cause local impacts, such as denuded vegetation, soil erosion, and permafrost thaw, but impacts on stream and watershed processes are less certain. In Wrangell-St. Elias National Park and Preserve (WRST), Alaska, ORV trails have caused local resource damage in intermountain lowlands with permafrost soils and abundant wetlands and there is a need to know whether these impacts are more extensive. Comparison of aerial photography from 1957, 1981, and 2004 coupled with ground surveys in 2009 reveal an increase in trail length and number and show an upslope expansion of a trail system around points of stream channel initiation. We hypothesized that these impacts could also cause premature initiation and headward expansion of channels because of lowered soil resistance and greater runoff accumulation as trails migrate upslope. Soil monitoring showed earlier and deeper thaw of the active layer in and adjacent to trails compared to reference sites. Several rainfall-runoff events during the summer of 2009 showed increased and sustained flow accumulation below trail crossings and channel shear forces sufficient to cause headward erosion of silt and peat soils. These observations of trail evolution relative to stream and wetland crossings together with process studies suggest that ORV trails are altering watershed processes. These changes in watershed processes appear to result in increasing drainage density and may also alter downstream flow regimes, water quality, and aquatic habitat. Addressing local land-use disturbances in boreal and arctic parklands with permafrost soils, such as WRST, where responses to climate change may be causing concurrent shifts in watershed processes, represents an important challenge facing resource managers

Cellular Bases of Barbiturate and Phenytoin Anticonvulsant Drug Action

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65509/1/j.1528-1157.1982.tb06093.x.pd

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

Ross, Macdonald, and a Theory for the Dynamics and Control of Mosquito-Transmitted Pathogens

Ronald Ross and George Macdonald are credited with developing a mathematical model of mosquito-borne pathogen transmission. A systematic historical review suggests that several mathematicians and scientists contributed to development of the Ross-Macdonald model over a period of 70 years. Ross developed two different mathematical models, Macdonald a third, and various “Ross-Macdonald” mathematical models exist. Ross-Macdonald models are best defined by a consensus set of assumptions. The mathematical model is just one part of a theory for the dynamics and control of mosquito-transmitted pathogens that also includes epidemiological and entomological concepts and metrics for measuring transmission. All the basic elements of the theory had fallen into place by the end of the Global Malaria Eradication Programme (GMEP, 1955–1969) with the concept of vectorial capacity, methods for measuring key components of transmission by mosquitoes, and a quantitative theory of vector control. The Ross-Macdonald theory has since played a central role in development of research on mosquito-borne pathogen transmission and the development of strategies for mosquito-borne disease prevention

Education and practice gaps on atrial fibrillation and anticoagulation: a survey of cardiovascular nurses

BACKGROUND: Patients’ knowledge of their atrial fibrillation (AF) and anticoagulation therapy are determinants of the efficacy of thromboprophylaxis. Nurses may be well placed to provide counselling and education to patients on all aspects of anticoagulation, including self-management. It is important that nurses are well informed to provide optimal education to patients. Current practice and knowledge of cardiovascular nurses on AF and anticoagulation in the Australian and New Zealand (ANZ) context is not well reported. This study aimed to; 1) Explore the nurse’s role in clinical decision making in anticoagulation in the setting of AF; 2) Describe perceived barriers and enablers to anticoagulation in AF; 3) Investigate practice patterns in the management of anticoagulation in the ANZ setting; 4) Assess cardiovascular nurses’ knowledge of anticoagulation. METHODS: A paper-based survey on current practices and knowledge of AF and anticoagulation was distributed during the Australian Cardiovascular Nursing College (ACNC) Annual Scientific Meeting, February 2014. This survey was also emailed to Cardiovascular Trials Nurses throughout New South Wales, Australia and nursing members of the Cardiac Society of Australia and New Zealand (CSANZ). RESULTS: There were 41/73 (56 %) respondents to the paper-based survey. A further 14 surveys were completed online via nurse members of the CSANZ, and via an investigator developed NSW cardiovascular trials nurse email distribution list. A total of 55 surveys were completed and included in analyses. Prior education levels on AF, stroke risk, anticoagulation and health behaviour modification were mixed. The CHA(2)DS(2)VASc and HAS-BLED risk stratification tools were reported to be underused by this group of clinicians. Reported key barriers to anticoagulation included; fears of patients falling, fears of poor adherence to medication taking and routine monitoring. Patient self-monitoring and self-management were reported as underutilised. ANZ cardiovascular nurses reported their key role to be counselling and advising patients on therapy regimens. Anticoagulant-drug interaction knowledge was generally poor. CONCLUSION: This study identified poor knowledge and practice in the areas of AF and anticoagulation. There is scope for improvement for cardiovascular nurses in ANZ in relation to AF and anticoagulation knowledge and practice