Learning Bayesian Networks with Thousands of Variables

We present a method for learning Bayesian networks from data sets containing thousands of variables without the need for structure constraints. Our approach is made of two parts. The first is a novel algorithm that effectively explores the space of possible parent sets of a node. It guides the exploration towards the most promising parent sets on the basis of an approximated score function that is computed in constant time. The second part is an improvement of an existing ordering-based algorithm for structure optimization. The new algorithm provably achieves a higher score compared to its original formulation. Our novel approach consistently outperforms the state of the art on very large data sets.

Comparison of optimal designs of steel portal frames including topological asymmetry considering rolled, fabricated and tapered sections

A structural design optimisation has been carried out to allow for asymmetry and fully tapered portal frames. The additional weight of an asymmetric structural shape was found to be on average 5–13% with additional photovoltaic (PV) loading having a negligible effect on the optimum design. It was also shown that fabricated and tapered frames achieved an average percentage weight reduction of 9% and 11%, respectively, as compared to comparable hot-rolled steel frames. When the deflection limits recommended by the Steel Construction Institute were used, frames were shown to be deflection controlled with industrial limits yielding up to 40% saving.

Quantitative structure-hydrophobicity relationships of molecular fragments and beyond

Quantitative structure-property relationship (QSPR) models were firstly established for the hydrophobic substituent constant (πX) using the theoretical descriptors derived solely from electrostatic potentials (EPSs) at the substituent atoms. The descriptors introduced are found to be related to hydrogen-bond basicity, hydrogen-bond acidity, cavity, or dipolarity/polarizability terms in linear solvation energy relationship, which endows the models good interpretability. The predictive capabilities of the models constructed were also verified by rigorous Monte Carlo cross-validation. Then, eight groups of meta- or para- disubstituted benzenes and one group of substituted pyridines were investigated. QSPR models for individual systems were achieved with the ESP-derived descriptors. Additionally, two QSPR models were also established for Rekker's fragment constants (foct), which is a secondary-treatment quantity and reflects average contribution of the fragment to logP. It has been demonstrated that the descriptors derived from ESPs at the fragments, can be well used to quantitatively express the relationship between fragment structures and their hydrophobic properties, regardless of the attached parent structure or the valence state. Finally, the relations of Hammett σ constant and ESP quantities were explored. It implies that σ and π, which are essential in classic QSAR and represent different type of contributions to biological activities, are also complementary in interaction site.

Host Defence Peptide LL-37; Effects of truncation on antimicrobial activity

Background: The oral cavity is an ideal environment for colonisation by micro-organisms. A first line of defence against microbial infection is the secretion of broad spectrum host defence peptides (HDPs). In the current climate of antibiotic resistance, exploiting naturally occurring HDPs or synthetic derivatives (mimetics) to combat infection is particularly appealing. The human cathelicidin, LL-37 is one such HDP expressed ubiquitously by epithelial cells and neutrophils. LL-37 exhibits the ability to bind lipopolysaccharide (LPS) and displays broad spectrum activity against a wide range of bacteria. The current study focuses on truncation of LL-37 and defining the antimicrobial and LPS binding activity of the resultant mimetics. Objectives: To assess the antimicrobial and LPS binding activity of LL-37 and three truncated mimetics (KE-18, EF-14 and KR-12). Methods: Peptides were synthesised in-house by Fmoc solid phase peptide synthesis or obtained commercially. Antimicrobial activity was determined using a radial diffusion assay and ability to bind LPS was determined by indirect ELISA. Results: LL-37 and mimetics displayed antimicrobial activity against Streptococcus mutans and Enterococcus Faecalis. KE-18 and KR-12 were shown to possess antimicrobial activity against both pathogens whereas EF-14 was the least antimicrobial. In terms of LPS binding, KE-18 and KR-12 were both effective whereas EF-14 showed the least activity of the three mimetics. Conclusion: Truncation of LL-37 can yield peptides which retain antimicrobial activities and have the ability to bind LPS. Interestingly in some cases the truncation of LL-37 produced mimetics with greater potency than the parent molecule in terms of antimicrobial activity and LPS binding. This work was funded by DEL and the Diabetes Wellness Foundation.

Effectiveness of a short message reminder in increasing compliance with pediatric cataract treatment:A randomized trial

Objective: Regular follow-up is essential to successful management of childhood cataract. We sought to assess whether a mobile phone short message service (SMS) for parents of children with cataract could improve follow-up adherence and the proportion of procedures performed in timely fashion. Design: Randomized, controlled trial. This trial is registered with ClinicalTrials.gov, NCT01417819. Participants: We included 258 parent-child pairs involved in the Childhood Cataract Program of the Chinese Ministry of Health. Methods: Participants were randomized (1:1) to a mobile phone SMS intervention or standard follow-up appointments. All participants were scheduled to attend <4 follow-up appointments according to the protocol. Parents in the intervention group received SMS automated reminders before scheduled appointments. The control group parents did not receive SMSs or any alternative reminder of scheduled appointments. Regular ocular examinations and analyses were performed by investigators masked to group allocation; however, study participants and the manager in charge of randomization and sending SMSs were not masked. Main Outcome Measures: Number of follow-up appointments attended, additional surgeries, laser treatments, changes in eyeglasses prescription, and occurrence of secondary ocular hypertension. Results: Among parent-child participants, 135 were randomly assigned to the SMS intervention and 123 to standard appointments. Attendance rates for the SMS group (first visit, 97.8%; second, 91.9%; third, 92.6%; fourth, 83%) were significantly higher than those for the control group (first visit, 87.8%; second, 69.9%; third, 56.9%; fourth, 33.3%). The increase in attendance rate for total number of follow-up visits with SMS reminders was 47.2% (relative risk [RR] for attendance, 1.47; 95% confidence interval [CI], 1.16-1.78; P = 0.003). The number needed to remind (NNR) to gain 1 additional visit by 1 child was 3 (95% CI, 1.8-4.2). A total of 247 clinical interventions were carried out in the SMS group and 134 in the control group (RR, 1.68; 95% CI, 1.37-1.99; P = 0.007). The NNR to result in 1 additional clinical intervention was 5 (95% CI, 3.5-6.5). Conclusions: The SMS reminders significantly improved follow-up adherence in pediatric cataract treatment. Using readily available mobile phone resources may be an effective and economic strategy to improve management of childhood cataract in China. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. © 2012 American Academy of Ophthalmology.

Effects of LL-37 Peptide Mimetics on Gingival Fibroblast Function

Host defence peptides, including the cathelicidin LL-37, play an important role in mucosal immunity, functioning as both antimicrobial agents and modulators of the inflammatory response. In the current climate of antibiotic resistance, the idea of using naturally occurring antimicrobial peptides, or their synthetic mimetics, to combat oral infection is particularly appealing. Objectives: The aim of this study was to investigate the effects of parent LL-37, and two peptide mimetics (KR-12 and KE-18), on cytokine expression and response to bacterial challenge by gingival fibroblasts. Methods: KR-12 and KE-18 are peptide mimetics of the biologically active, mid-region sequence of LL-37. The effects of commercially available LL-37, KR-12 and KE-18 on gingival fibroblast response to E coli and P gingivalis LPS challenge, analysed by IL-6 and IL-8 expression, were determined in cell culture by ELISA. The direct effects of each peptide on IL-6, IL-8, CXCL-1 and HGF expression were also determined by ELISA. The MTT assay was used to evaluate peptide effects on fibroblast viability. Results: LL-37 and KE-18, but not KR-12, inhibited LPS induction of inflammatory cytokine expression and directly stimulated CXCL-1 production by fibroblasts. All 3 peptides stimulated production of IL-8 and HGF. Neither LL-37 nor KE-12 affected cell viability, while KE-18, at higher concentrations, induced cell death. Conclusions: Shorter, peptide mimetics of LL-37, in particular KE-18, retain the immunomodulatory effects of the parent molecule and possess excellent potential as therapeutic agents in the treatment of oral infections including periodontal disease.

LL-37 Degradation by GCF: A Role for Porphyromonas gingivalis Proteinases?

Background: LL-37, composed of 37 amino acid residues, is an innate host defence peptide of the cathelicidin family. It is expressed by neutrophils, monocytes and epithelial cells and exhibits both anti-bacterial and immunomodulatory properties. LL-37 is however prone to proteolytic degradation by proteinases, thus potentially limiting its inherent host defence properties in the inflammatory milieu. Objectives: The present study was designed to determine whether LL-37 was degraded by components of gingival crevicular fluid (GCF) from healthy subjects or those with periodontitis. In addition, we aimed to deduce whether degradation of the peptide was accelerated in GCF samples which were determined to be positive for the periodontopathic bacterium Porphyromonas gingivalis. Methods: GCF and bacterial plaque samples, pre- and post non-surgical periodontal treatment, were collected from 4 individual sites in patients presenting with advanced periodontitis. In healthy subjects, GCF samples only were collected. Plaque samples were analysed by QPCR for the presence or absence of P. gingivalis. Pooled GCF samples from healthy sites; periodontitis sites which were P. gingivalis negative (Pg-); or periodontitis sites which were P. gingivalis positive (Pg+), were incubated with synthetic LL-37 for 0 – 180 min. The degradation products were then analysed by matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS). Results: LL-37 was not degraded when incubated with GCF from healthy subjects. In contrast, LL-37 was degraded after 30 min when incubated with Pg- GCF. However degradation of LL-37 was apparent after only 2 min incubation with Pg+ GCF and the parent molecule was almost completely degraded after 30 min. Conclusions: The rapid degradation of LL-37, particularly in Pg+ sites, highlights the limited role which this host defence peptide may play in the presence of biologically active proteinases. It also underscores a potent virulence mechanism of P. gingivalis used to circumvent innate host responses.

Spectacle acceptance among secondary school students in rural China: the Xichang Pediatric Refractive Error Study (X-PRES)--report 5.

PURPOSE: To assess determinants of spectacle acceptance and use among rural Chinese children. METHODS: Children with uncorrected acuity < or = 6/12 in either eye and whose presenting vision could be improved > or = 2 lines with refraction were identified from a school-based sample of 1892 students. Information on obtaining glasses and the benefits of spectacles was provided to children, families, and teachers. Purchase of new spectacles and reasons for nonpurchase were assessed by direct inspection and interview 3 months later. RESULTS: Among 674 (35.6%) children requiring spectacles (mean age, 14.7 +/- 0.8 years), 597 (88.6%) were followed up. Among 339 children with no glasses at baseline, 30.7% purchased spectacles, whereas 43.2% of 258 children with inaccurate glasses replaced them. Most (70%) subjects paid US$13 to $26. Among children with bilateral vision < or = 6/18, 45.6% bought glasses. In multivariate models, presenting vision < 6/12 (P < 0.009), refractive error < -2.0 D (P < 0.001), and amount willing to pay for glasses (P = 0.01) were predictors of purchase. Reasons for nonpurchase included satisfaction with current vision (78% of those with glasses at baseline, 49% of those without), concerns over price or parental refusal (18%), and fear glasses would weaken the eyes (13%). Only 26% of children stated that they usually wore their new glasses. CONCLUSIONS: Many families in rural China will pay for glasses, though spectacle acceptance was < 50%, even among children with poor vision. Acceptance could be improved by price reduction, education showing that glasses will not harm the eyes, and parent-focused interventions.

Parenthood and Open Adoption: an Interpretative Phenomenological Analysis

This book explores what it is like to be involved in contemporary open adoption, characterised by varying forms of contact with birth relatives, from an adoptive parent point of view.

The author’s fine-grained interpretative phenomenological analysis of adopters’ accounts reveals the complexity of kinship for those whose most significant relationships are made, unmade and permanently altered through adoption. MacDonald distinctively connects adoption to wider sociological theories of relatedness and personal life, and focuses on domestic non-kin adoption of children from state care, including compulsory adoption. The book also addresses current child welfare concerns, and suggestions are made for adoption practice. The book will be of interest to scholars and students with an interest in adoption, social work, child welfare, foster care, family and sociology.

Availability and transfer to grain of As, Cd, Cu, Ni, Pb and Zn in a barley agri-system: Impact of biochar, organic and mineral fertilizers

With biochar becoming an emerging soil amendment and a tool to mitigate climate change, there are only a few studies documenting its effects on trace element cycling in agriculture. Zn and Cu are deficient in many human diets, whilst exposures to As, Pb and Cd need to be decreased. Biochar has been shown to affect many of them mainly at a bench or greenhouse scale, but field research is not available. In our experiment we studied the impact of biochar, as well as its interactions with organic (compost and sewage sludge) and mineral fertilisers (NPK and nitrosulfate), on trace element mobility in a Mediterranean agricultural field (east of Madrid, Spain) cropped with barley. At harvesting time, we analysed the soluble fraction, the available fraction (assessed with the diffusive gradients in thin gels technique, DGT) and the concentration of trace elements in barley grain. No treatment was able to significantly increase Zn, Cu or Ni concentration in barley grain, limiting the application for cereal fortification. Biochar helped to reduce Cd and Pb in grain, whereas As concentration slightly increased. Overall biochar amendments demonstrated a potential to decrease Cd uptake in cereals, a substantial pathway of exposure in the Spanish population, whereas mineral fertilisation and sewage sludge increased grain Cd and Pb. In the soil, biochar helped to stabilise Pb and Cd, while marginally increasing As release/mobilisation. Some of the fertilisation practises or treatments increased toxic metals and As solubility in soil, but never to an extent high enough to be considered an environmental risk. Future research may try to fortify Zn, Cu and Ni using other combinations of organic amendments and different parent biomass to produce enriched biochars.

Sexual Abuse in Malawi: Patterns of Disclosure

Potential human immunodeficiency virus transmission makes prompt disclosure of child sexual abuse in Africa critical. The pattern of disclosure of 133 children presenting to the largest hospital in Malawi were analyzed. Eighty percent presented early enough for effective use of HIV postexposure prophylaxis. Seventy-five percent of children made a disclosure of child sexual abuse; 29% spontaneously and 47% after prompting. Disclosures were most commonly made to a parent, and age did not affect the pattern of disclosure. The number of children reporting child sexual abuse is increasing, possibly because of increasing awareness, availability of services, and fear of HIV. Although prompt disclosure rates were relatively high, facilitating easier disclosure of child sexual abuse by a free telephone help-line and better training of teachers may be helpful. 

Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters.

Electron impact fragmentation of thymine:partial ionization cross sections for positive fragments

We have measured mass spectra for positive ions for low-energy electron impact on thymine using a reflectron time-of-flight mass spectrometer. Using computer controlled data acquisition, mass spectra have been acquired for electron impact energies up to 100 eV in steps of 0.5 eV. Ion yield curves for most of the fragment ions have been determined by fitting groups of adjacent peaks in the mass spectra with sequences of normalized Gaussians. The ion yield curves have been normalized by comparing the sum of the ion yields to the average of calculated total ionization cross sections. Appearance energies have been determined. The nearly equal appearance energies of 83 u and 55 u observed in the present work strongly indicate that near threshold the 55 u ion is formed directly by the breakage of two bonds in the ring, rather than from a successive loss of HNCO and CO from the parent ion. Likewise 54 u is not formed by CO loss from 82 u. The appearance energies are in a number of cases consistent with the loss of one or more hydrogen atoms from a heavier fragment, but 70 u is not formed by hydrogen loss from 71 u.

Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12 years

OBJECTIVE: To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks' gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years.

METHODS: Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years of age, all children were assessed under standardised conditions at Queen's University, Belfast, UK to determine cognitive and behavioural outcomes using the British Ability Score-II and Achenbach Child Behavioural Checklist Parent Rated Version under standardised conditions. Regression analysis was performed, controlling for confounders such as gender, socioeconomic status and age at assessment.

RESULTS: The mean age of follow-up was 12.4 years (±0.5 SD) with 44% of children male (n=63). When UAD was assessed at 28 weeks, the elevated fetal UAD group had lower scores in cognitive assessments of information processing and memory. Parameters included (1) recall of objects immediate verbal (p=0.002), (2) delayed verbal (p=0.008) and (3) recall of objects immediate spatial (p=0.0016). There were no significant differences between the Doppler groups at 32 or 34 weeks' gestation.

CONCLUSIONS: An elevated UAD PI at 28 weeks' gestation in the absence of FGR or prematurity is associated with lower scores of declarative memory in children aged 12 years. A potential explanation for this is an element of placental insufficiency in the presence of the appropriately grown fetus, which affects the development of the fetal hippocampus and information processing and memory long-term. These findings, however, had no impact on overall academic ability, mental processing and reasoning or overall behavioural function.

Imagined and occasional co-presence in open adoption: how adoptive parents mediate birth connections.

This chapter explores the ways that adopted children and their birth parents can remain co-present following adoption. It focuses specifically on public adoption of children who have been in the care of child welfare services, and draws on adoptive parents’ accounts of their experiences of adoption openness. The distinctive features of co-presence between children and their birth parents after adoption are: that it is mediated by negotiated contact agreements and through on-going adoptive family practices; and that it is occasional, with its infrequency displaying the status and significance of birth relationships. Physical co-presence can in some cases be achieved through face-to-face contact meetings, however, even when this not possible, birth parents can be present in the hearts and minds of the adoptive family, constituting a form of imagined co-presence. The chapter explores how adopters achieve, delimit and mediate imagined and physical co-presence between their child and birth parent and concludes by considering the emergence of virtual co-presence via online social media.