Narrative-based computational modelling of the Gp130/JAK/STAT signalling pathway.

BACKGROUND: Appropriately formulated quantitative computational models can support researchers in understanding the dynamic behaviour of biological pathways and support hypothesis formulation and selection by "in silico" experimentation. An obstacle to widespread adoption of this approach is the requirement to formulate a biological pathway as machine executable computer code. We have recently proposed a novel, biologically intuitive, narrative-style modelling language for biologists to formulate the pathway which is then automatically translated into an executable format and is, thus, usable for analysis via existing simulation techniques. RESULTS: Here we use a high-level narrative language in designing a computational model of the gp130/JAK/STAT signalling pathway and show that the model reproduces the dynamic behaviour of the pathway derived by biological observation. We then "experiment" on the model by simulation and sensitivity analysis to define those parameters which dominate the dynamic behaviour of the pathway. The model predicts that nuclear compartmentalisation and phosphorylation status of STAT are key determinants of the pathway and that alternative mechanisms of signal attenuation exert their influence on different timescales. CONCLUSION: The described narrative model of the gp130/JAK/STAT pathway represents an interesting case study showing how, by using this approach, researchers can model biological systems without explicitly dealing with formal notations and mathematical expressions (typically used for biochemical modelling), nevertheless being able to obtain simulation and analysis results. We present the model and the sensitivity analysis results we have obtained, that allow us to identify the parameters which are most sensitive to perturbations. The results, which are shown to be in agreement with existing mathematical models of the gp130/JAK/STAT pathway, serve us as a form of validation of the model and of the approach itself

Pregnant women\u27s alcohol consumption : the predictive utility of intention to drink and prepregnancy drinking behaviour

Objective: This study had two aims: (1) to examine pregnant women\u27s alcohol consumption across time from prepregnancy until childbirth and (2) to explore whether prepregnancy drinking and intention to drink predict prenatal alcohol consumption while controlling for relevant demographic variables.Methods: At 17&ndash;21 weeks, 248 pregnant women completed questions about demographics, intention to drink alcohol during the subsequent pregnancy, and retrospective measures of prepregnancy and early pregnancy consumption. After this time, calendars were sent fortnightly assessing daily alcohol consumption until birth.Results: For women who drank both prepregnancy and postpregnancy confirmation, average fortnight alcohol consumption in the first weeks of pregnancy was lower than during prepregnancy, and consumption continued to decrease between gestational weeks 1 and 8, particularly following pregnancy confirmation, after which it remained relatively stable. When predicting whether women drank in late pregnancy, intention accounted for unique variance after controlling for income and prepregnancy drinking. For women who drank after pregnancy confirmation, prepregnancy drinking quantity significantly predicted intention to drink, which in turn predicted fortnight alcohol consumption in later pregnancy, after controlling for prepregnancy drinking and income.Conclusions: Findings highlight the need to measure alcohol consumption at multiple time points across pregnancy, the need for educating and supporting women to reduce consumption when planning pregnancies, and the usefulness of intention to drink as a predictor of drinking during pregnancy.<br /

Therapeutic affordances of online support group use in women with endometriosis

Background: The Internet has provided women living with endometriosis new opportunities to seek support online. Online support groups may provide a range of therapeutic affordances which may benefit these women. Objective: To examine the presence of therapeutic affordances as perceived by women who use endometriosis online support groups. Methods: Sixty-nine women (aged 19 to 50 years; Mean = 34.2; 65.2% UK; 21.7% USA) participated in an online interview exploring online support group use. Participants had been using online support groups on average 2 years and 4 months (Range = 1 month to 14 years, 9 months). Responses were analysed using inductive thematic analysis. Results: The analysis revealed 4 therapeutic affordances related to online support group use; i) “connection” i.e. the ability to connect in order to support each other, exchange advice, and to try to overcome feelings of loneliness; ii) “exploration” i.e. the ability to look for information, learn and bolster their knowledge; iii) “narration” i.e. the ability to share their experiences, as well as read about the experiences of others; and iv) “self-presentation” i.e. the ability to manage how they present themselves online. The associated outcomes of use were predominantly positive, such as reassurance and improved coping. However, a number of negative aspects were revealed including: concerns about the accuracy of information, arguments between members, over-reliance on the group, becoming upset by negative experiences or good news items and confidentiality of personal information. Conclusions: Our findings support the SCENA model (Self-presentation, Connection, Exploration, Narration and Adaptation) proposed by Merolli et al., (2014) and reveal a range of positive aspects that may benefit members, particularly in relation to reassurance and coping. However, negative aspects need to be addressed in order to maximise the potential benefit of support groups. Some of these can be addressed relatively easily through making privacy policies clearer, including health professionals to moderate content and structuring forums to encourage the sharing of positive stories

Effectiveness of early intervention programs for parents of preterm infants: a meta-review of systematic reviews

Background: Various intervention programs exist for parents of preterm babies and some systematic reviews (SRs) have synthesised the evidence of their effectiveness. These reviews are, however, limited to specific interventions, components, or outcomes, and a comprehensive evidence base is lacking. The aim of this meta-review was to appraise and meta-synthesise the evidence from existing SRs to provide a comprehensive evidence base on the effectiveness of interventions for parents of preterm infants on parental and infant outcomes. Methods: We conducted a comprehensive search of the following databases to identify relevant SRs: Cochrane library, Web of science, EMBASE, CINAHL, British Nursing Index, PsycINFO, Medline, ScienceDirect, Scopus, IBSS, DOAJ, ERIC, EPPI-Centre, PROSPERO, WHO Library. Additional searches were conducted using authors’ institutional libraries, Google Scholar, and the reference lists of identified reviews. Identified articles were screened in two stages against an inclusion criteria with titles and abstracts screened first followed by full-text screening. Selected SRs were appraised using the AMSTAR tool. Extracted data using a predesigned tool were synthesised narratively examining the direction of impact on outcomes. Results: We found 11 SRs eligible for inclusion that synthesised a total of 343 quantitative primary studies. The average quality of the SRs was ‘medium’. Thirty four interventions were reported across the SRs with considerable heterogeneity in the structural framework and the targeted outcomes that included maternal-infant dyadic, maternal/parental, and infant outcomes. Among all interventions, Kangaroo Care (KC) showed the most frequent positive impact across outcomes (n = 19) followed by Mother Infant Transaction Program (MITP) (n = 14). Other interventions with most consistent positive impact on infant outcomes were Modified-Mother Infant Transaction Program (M-MITP) (n = 6), Infant Health and Development Program (IHDP) (n = 5) and Creating Opportunities for Parent Empowerment (COPE) (n = 5). Overall, interventions with both home and facility based components showed the most frequent positive impact across outcomes. Conclusions: Neonatal care policy and planning for preterm babies should consider the implementation of interventions with most positive impact on outcomes. The heterogeneity in interventions and outcomes calls for the development and implementation of an integrated program for parents of preterm infants with a clearly defined global set of parental and infant outcomes

Confronting Standard Models of Proto–Planetary Disks With New Mid–Infrared Sizes from the Keck Interferometer

This is the final version of the article. Available from American Astronomical Society via the DOI in this record.The accepted author manuscript is in ORE at http://hdl.handle.net/10871/21611We present near- and mid-infrared (MIR) interferometric observations made with the Keck Interferometer Nuller and near-contemporaneous spectro-photometry from the infrared telescope facilities (IRTFs) of 11 well-known young stellar objects, several of which were observed for the first time in these spectral and spatial resolution regimes. With au-level spatial resolution, we first establish characteristic sizes of the infrared emission using a simple geometrical model consisting of a hot inner rim and MIR disk emission. We find a high degree of correlation between the stellar luminosity and the MIR disk sizes after using near-infrared data to remove the contribution from the inner rim. We then use a semi-analytical physical model to also find that the very widely used "star + inner dust rim + flared disk" class of models strongly fails to reproduce the spectral energy distribution (SED) and spatially resolved MIR data simultaneously; specifically a more compact source of MIR emission is required than results from the standard flared disk model. We explore the viability of a modification to the model whereby a second dust rim containing smaller dust grains is added, and find that the 2-rim model leads to significantly improved fits in most cases. This complexity is largely missed when carrying out SED modeling alone, although detailed silicate feature fitting by McClure et al. recently came to a similar conclusion. As has been suggested recently by Menu et al., the difficulty in predicting MIR sizes from the SED alone might hint at "transition disk"-like gaps in the inner au; however, the relatively high correlation found in our MIR disk size versus stellar luminosity relation favors layered disk morphologies and points to missing disk model ingredients instead.M.S. was supported by NASA ADAP grant NNX09AC73G. R.W.R. was supported by the IR&D program of The Aerospace Corporation

Host-pathogen coevolution increases genetic variation in susceptibility to infection

It is common to find considerable genetic variation in susceptibility to infection in natural populations. We have investigated whether natural selection increases this variation by testing whether host populations show more genetic variation in susceptibility to pathogens that they naturally encounter than novel pathogens. In a large cross-infection experiment involving four species of Drosophila and four host-specific viruses, we always found greater genetic variation in susceptibility to viruses that had coevolved with their host. We went on to examine the genetic architecture of resistance in one host species, finding that there are more major-effect genetic variants in coevolved host-pathogen interactions. We conclude that selection by pathogens has increased genetic variation in host susceptibility, and much of this effect is caused by the occurrence of major-effect resistance polymorphisms within populations

Cross-sectional associations between sleep duration, sedentary time, physical activity, and adiposity indicators among Canadian preschool-aged children using compositional analyses

Abstract Background Sleep duration, sedentary behaviour, and physical activity are three co-dependent behaviours that fall on the movement/non-movement intensity continuum. Compositional data analyses provide an appropriate method for analyzing the association between co-dependent movement behaviour data and health indicators. The objectives of this study were to examine: (1) the combined associations of the composition of time spent in sleep, sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) with adiposity indicators; and (2) the association of the time spent in sleep, sedentary behaviour, LPA, or MVPA with adiposity indicators relative to the time spent in the other behaviours in a representative sample of Canadian preschool-aged children. Methods Participants were 552 children aged 3 to 4 years from cycles 2 and 3 of the Canadian Health Measures Survey. Sedentary time, LPA, and MVPA were measured with Actical accelerometers (Philips Respironics, Bend, OR USA), and sleep duration was parental reported. Adiposity indicators included waist circumference (WC) and body mass index (BMI) z-scores based on World Health Organization growth standards. Compositional data analyses were used to examine the cross-sectional associations. Results The composition of movement behaviours was significantly associated with BMI z-scores (p = 0.006) but not with WC (p = 0.718). Further, the time spent in sleep (BMI z-score: γ sleep  = −0.72; p = 0.138; WC: γ sleep  = −1.95; p = 0.285), sedentary behaviour (BMI z-score: γ SB  = 0.19; p = 0.624; WC: γ SB  = 0.87; p = 0.614), LPA (BMI z-score: γ LPA  = 0.62; p = 0.213, WC: γ LPA  = 0.23; p = 0.902), or MVPA (BMI z-score: γ MVPA  = −0.09; p = 0.733, WC: γ MVPA  = 0.08; p = 0.288) relative to the other behaviours was not significantly associated with the adiposity indicators. Conclusions This study is the first to use compositional analyses when examining associations of co-dependent sleep duration, sedentary time, and physical activity behaviours with adiposity indicators in preschool-aged children. The overall composition of movement behaviours appears important for healthy BMI z-scores in preschool-aged children. Future research is needed to determine the optimal movement behaviour composition that should be promoted in this age group

Utilisation of sexual health services by female sex workers in Nepal

Background The Nepal Demographic Health Survey (NDHS) in 2006 showed that more than half (56%) of the women with sexually transmitted infections (STIs), including HIV, in Nepal sought sexual health services. There is no such data for female sex workers (FSWs) and the limited studies on this group suggest they do not even use routine health services. This study explores FSWs use of sexual health services and the factors associated with their use and non-use of services. Methods This study aimed to explore the factors associated with utilisation of sexual health services by FSWs in the Kathmandu Valley of Nepal, and it used a mixed-method approach consisting of an interviewer administered questionnaire-based survey and in-depth interviews. Results The questionnaire survey, completed with 425 FSWs, showed that 90% FSWs self-reported sickness, and (30.8%) reported symptoms of STIs. A quarter (25%) of those reporting STIs had never visited any health facilities especially for sexual health services preferring to use non-governmental clinics (72%), private clinics (50%), hospital (27%) and health centres (13%). Multiple regression analysis showed that separated, married and street- based FSWs were more likely to seek health services from the clinics or hospitals. In- depth interviews with 15 FSWs revealed that FSWs perceived that personal, structural and socio-cultural barriers, such as inappropriate clinic opening hours, discrimination, the judgemental attitude of the service providers, lack of confidentiality, fear of public exposure, and higher fees for the services as barriers to their access and utilisation of sexual health services. Conclusion FSWs have limited access to information and to health services, and operate under personal, structural and socio-cultural constraints. The ‘education’ to change individual behaviour, health worker and community perceptions, as well as the training of the health workers, is necessary

Ultra-Sensitive Hot-Electron Nanobolometers for Terahertz Astrophysics

The background-limited spectral imaging of the early Universe requires spaceborne terahertz (THz) detectors with the sensitivity 2-3 orders of magnitude better than that of the state-of-the-art bolometers. To realize this sensitivity without sacrificing operating speed, novel detector designs should combine an ultrasmall heat capacity of a sensor with its unique thermal isolation. Quantum effects in thermal transport at nanoscale put strong limitations on the further improvement of traditional membrane-supported bolometers. Here we demonstrate an innovative approach by developing superconducting hot-electron nanobolometers in which the electrons are cooled only due to a weak electron-phonon interaction. At T<0.1K, the electron-phonon thermal conductance in these nanodevices becomes less than one percent of the quantum of thermal conductance. The hot-electron nanobolometers, sufficiently sensitive for registering single THz photons, are very promising for submillimeter astronomy and other applications based on quantum calorimetry and photon counting.Comment: 19 pages, 3 color figure

Variability of disk emission in pre-main sequence and related stars. II. Variability in the gas and dust emission of the Herbig Fe star SAO 206462

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.We present 13 epochs of near-infrared (0.8-5 μm) spectroscopic observations of the pre-transitional, "gapped" disk system in SAO 206462 (=HD 135344B). In all, six gas emission lines (Brα, Brγ, Paβ, Paγ, Paδ, Paepsilon, and the 0.8446 μm line of O I) along with continuum measurements made near the standard J, H, K, and L photometric bands were measured. A mass accretion rate of approximately 2 × 10–8 M ☉ yr–1 was derived from the Brγ and Paβ lines. However, the fluxes of these lines varied by a factor of over two during the course of a few months. The continuum also varied, but by only ~30%, and even decreased at a time when the gas emission was increasing. The H I line at 1.083 μm was also found to vary in a manner inconsistent with that of either the hydrogen lines or the dust. Both the gas and dust variabilities indicate significant changes in the region of the inner gas and the inner dust belt that may be common to many young disk systems. If planets are responsible for defining the inner edge of the gap, they could interact with the material on timescales commensurate with what is observed for the variations in the dust, while other disk instabilities (thermal, magnetorotational) would operate there on longer timescales than we observe for the inner dust belt. For SAO 206462, the orbital period would likely be 1-3 years. If the changes are being induced in the disk material closer to the star than the gap, a variety of mechanisms (disk instabilities, interactions via planets) might be responsible for the changes seen. The He I feature is most likely due to a wind whose orientation changes with respect to the observer on timescales of a day or less. To further constrain the origin of the gas and dust emission will require multiple spectroscopic and interferometric observations on both shorter and longer timescales that have been sampled so far.This work was supported by NASA ADP grants NNH06CC28C and NNX09AC73G, Hubble Space Telescope grants HST-GO-10764 and HST-GO-10864, Chilean National TAC grants CNTAC-010A-064