Kepler Observations of V447 Lyr: An Eclipsing U Gem Cataclysmic Variable

We present the results of an analysis of data covering 1.5 years of the dwarf nova V447 Lyr. We detect eclipses of the accretion disk by the mass donating secondary star every 3.74 hrs which is the binary orbital period. V447 Lyr is therefore the first dwarf nova in the Kepler field to show eclipses. We also detect five long outbursts and six short outbursts showing V447 Lyr is a U Gem type dwarf nova. We show that the orbital phase of the mid-eclipse occurs earlier during outbursts compared to quiescence and that the width of the eclipse is greater during outburst. This suggests that the bright spot is more prominent during quiescence and that the disk is larger during outburst than quiescence. This is consistent with an expansion of the outer disk radius due to the presence of high viscosity material associated with the outburst, followed by a contraction in quiescence due to the accretion of low angular momentum material. We note that the long outbursts appear to be triggered by a short outburst, which is also observed in the super-outbursts of SU UMa dwarf novae as observed using Kepler.Comment: Accepted by MNRA

Training community healthcare workers on the use of information and communication technologies: a randomised controlled trial of traditional versus blended learning in Malawi, Africa.

BACKGROUND: Despite the increasing uptake of information and communication technologies (ICT) within healthcare services across developing countries, community healthcare workers (CHWs) have limited knowledge to fully utilise computerised clinical systems and mobile apps. The 'Introduction to Information and Communication Technology and eHealth' course was developed with the aim to provide CHWs in Malawi, Africa, with basic knowledge and computer skills to use digital solutions in healthcare delivery. The course was delivered using a traditional and a blended learning approach. METHODS: Two questionnaires were developed and tested for face validity and reliability in a pilot course with 20 CHWs. Those were designed to measure CHWs' knowledge of and attitudes towards the use of ICT, before and after each course, as well as their satisfaction with each learning approach. Following validation, a randomised controlled trial was conducted to assess the effectiveness of the two learning approaches. A total of 40 CHWs were recruited, stratified by position, gender and computer experience, and allocated to the traditional or blended learning group using block randomisation. Participants completed the baseline and follow-up questionnaires before and after each course to assess the impact of each learning approach on their knowledge, attitudes, and satisfaction. Per-item, pre-post and between-group, mean differences for each approach were calculated using paired and unpaired t-tests, respectively. Per-item, between-group, satisfaction scores were compared using unpaired t-tests. RESULTS: Scores across all scales improved after attending the traditional and blended learning courses. Self-rated ICT knowledge was significantly improved in both groups with significant differences between groups in seven domains. However, actual ICT knowledge scores were similar across groups. There were no significant differences between groups in attitudinal gains. Satisfaction with the course was generally high in both groups. However, participants in the blended learning group found it more difficult to follow the content of the course. CONCLUSIONS: This study shows that there is no difference between blended and traditional learning in the acquisition of actual ICT knowledge among community healthcare workers in developing countries. Given the human resource constraints in remote resource-poor areas, the blended learning approach may present an advantageous alternative to traditional learning

V344 Lyrae: A Touchstone SU UMa Cataclysmic Variable in the Kepler Field

We report on the analysis of the Kepler short-cadence (SC) light curve of V344 Lyr obtained during 2009 June 20 through 2010 Mar 19 (Q2--Q4). The system is an SU UMa star showing dwarf nova outbursts and superoutbursts, and promises to be a touchstone for CV studies for the foreseeable future. The system displays both positive and negative superhumps with periods of 2.20 and 2.06-hr, respectively, and we identify an orbital period of 2.11-hr. The positive superhumps have a maximum amplitude of ~0.25-mag, the negative superhumps a maximum amplitude of ~0.8 mag, and the orbital period at quiescence has an amplitude of ~0.025 mag. The quality of the Kepler data is such that we can test vigorously the models for accretion disk dynamics that have been emerging in the past several years. The SC data for V344 Lyr are consistent with the model that two physical sources yield positive superhumps: early in the superoutburst, the superhump signal is generated by viscous dissipation within the periodically flexing disk, but late in the superoutburst, the signal is generated as the accretion stream bright spot sweeps around the rim of the non-axisymmetric disk. The disk superhumps are roughly anti-phased with the stream/late superhumps. The V344 Lyr data also reveal negative superhumps arising from accretion onto a tilted disk precessing in the retrograde direction, and suggest that negative superhumps may appear during the decline of DN outbursts. The period of negative superhumps has a positive dP/dt in between outbursts.Comment: ApJ, In Press (20 pages, 27 figures) A version with full-resolution figures is available at http://www.astro.fit.edu/wood/WoodV344.pd

Superhumps in Cataclysmic Binaries. XXIII. V442 Ophiuchi and RX J1643.7+3402

We report the results of long observing campaigns on two novalike variables: V442 Ophiuchi and RX J1643.7+3402. These stars have high-excitation spectra, complex line profiles signifying mass loss at particular orbital phases, and similar orbital periods (respectively 0.12433 and 0.12056 d). They are well-credentialed members of the SW Sex class of cataclysmic variables. Their light curves are also quite complex. V442 Oph shows periodic signals with periods of 0.12090(8) and 4.37(15) days, and RX J1643.7+3402 shows similar signals at 0.11696(8) d and 4.05(12) d. We interpret these short and long periods respectively as a "negative superhump" and the wobble period of the accretion disk. The superhump could then possibly arise from the heating of the secondary (and structures fixed in the orbital frame) by inner-disk radiation, which reaches the secondary relatively unimpeded since the disk is not coplanar. At higher frequencies, both stars show another type of variability: quasi-periodic oscillations (QPOs) with a period near 1000 seconds. Underlying these strong signals of low stability may be weak signals of higher stability. Similar QPOs, and negative superhumps, are quite common features in SW Sex stars. Both can in principle be explained by ascribing strong magnetism to the white dwarf member of the binary; and we suggest that SW Sex stars are borderline AM Herculis binaries, usually drowned by a high accretion rate. This would provide an ancestor channel for AM Hers, whose origin is still mysterious.Comment: PDF, 41 pages, 4 tables, 16 figures; accepted, in press, to appear December 2002, PASP; more info at http://cba.phys.columbia.edu

Developing Consensus-Based Priority Outcome Domains for Trials in Kidney Transplantation:A Multinational Delphi Survey With Patients, Caregivers, and Health Professionals

Background: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision-making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. Methods: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During Round 2 and 3, participants re-rated the outcomes after reviewing their own score, the distribution of the respondents’ scores, and comments. We calculated the median, mean, and proportion rating 7-9 (critically important), and analyzed comments thematically. Results: 1018 participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed Round 1, and 779 (77%) completed Round 3. The top eight outcomes that met the consensus criteria in Round 3 (mean ≥7.5, median ≥8 and proportion >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin) and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to six outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified five themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. Conclusions: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Therapeutic targeting of cathepsin C::from pathophysiology to treatment

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials

Post-primary students' images of mathematics: a focus on the qualitative data

A questionnaire survey was conducted as part of a PhD study investigating post-primary students' images of mathematics in Ireland. A definition of image of mathematics was adopted from Lim (1999) and Wilson (2011). Students' images of mathematics were hypothesized to include attitudes, beliefs, motivation, self-concept, emotions and past experiences regarding mathematics. A questionnaire was created with both quantitative and qualitative aspects. This paper focuses on the qualitative facet by reviewing students' responses to the open-ended questions according to the five categories of image of mathematics found by Lim (1999). The qualitative data provides a more in-depth insight into Irish students' images of mathematics. Findings from the qualitative data afford an innovative insight into post-primary mathematics education from the student perspective, thus offering a means for mathematics educators to respond to students' needs and encourage Irish post-primary students' engagement with mathematics