Template-Stripped Multifunctional Wedge and Pyramid Arrays for Magnetic Nanofocusing and Optical Sensing

We present large-scale reproducible fabrication of multifunctional ultrasharp metallic structures on planar substrates with capabilities including magnetic field nanofocusing and plasmonic sensing. Objects with sharp tips such as wedges and pyramids made with noble metals have been extensively used for enhancing local electric fields via the lightning-rod effect or plasmonic nanofocusing. However, analogous nanofocusing of magnetic fields using sharp tips made with magnetic materials has not been widely realized. Reproducible fabrication of sharp tips with magnetic as well as noble metal layers on planar substrates can enable straightforward application of their material and shape-derived functionalities. We use a template-stripping method to produce plasmonic-shell-coated nickel wedge and pyramid arrays at the wafer-scale with tip radius of curvature close to 10 nm. We further explore the magnetic nanofocusing capabilities of these ultrasharp substrates, deriving analytical formulas and comparing the results with computer simulations. These structures exhibit nanoscale spatial control over the trapping of magnetic microbeads and nanoparticles in solution. Additionally, enhanced optical sensing of analytes by these plasmonic-shell-coated substrates is demonstrated using surface-enhanced Raman spectroscopy. These methods can guide the design and fabrication of novel devices with applications including nanoparticle manipulation, biosensing, and magnetoplasmonics

Improved genetically-encoded, FlincG-type fluorescent biosensors for neural cGMP imaging.

Genetically-encoded biosensors are powerful tools for understanding cellular signal transduction mechanisms. In aiming to investigate cGMP signaling in neurones using the EGFP-based fluorescent biosensor, FlincG (fluorescent indicator for cGMP), we encountered weak or non-existent fluorescence after attempted transfection with plasmid DNA, even in HEK293T cells. Adenoviral infection of HEK293T cells with FlincG, however, had previously proved successful. Both constructs were found to harbor a mutation in the EGFP domain and had a tail of 17 amino acids at the C-terminus that differed from the published sequence. These discrepancies were systematically examined, together with mutations found beneficial for the related GCaMP family of Ca(2+) biosensors, in a HEK293T cell line stably expressing both nitric oxide (NO)-activated guanylyl cyclase and phosphodiesterase-5. Restoring the mutated amino acid improved basal fluorescence whereas additional restoration of the correct C-terminal tail resulted in poor cGMP sensing as assessed by superfusion of either 8-bromo-cGMP or NO. Ultimately, two improved FlincGs were identified: one (FlincG2) had the divergent tail and gave moderate basal fluorescence and cGMP response amplitude and the other (FlincG3) had the correct tail, a GCaMP-like mutation in the EGFP region and an N-terminal tag, and was superior in both respects. All variants tested were strongly influenced by pH over the physiological range, in common with other EGFP-based biosensors. Purified FlincG3 protein exhibited a lower cGMP affinity (0.89 μM) than reported for the original FlincG (0.17 μM) but retained rapid kinetics and a 230-fold selectivity over cAMP. Successful expression of FlincG2 or FlincG3 in differentiated N1E-115 neuroblastoma cells and in primary cultures of hippocampal and dorsal root ganglion cells commends them for real-time imaging of cGMP dynamics in neural (and other) cells, and in their subcellular specializations

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

Improving chlamydia knowledge should lead to increased chlamydia testing among Australian general practitioners: a cross-sectional study of chlamydia testing uptake in general practice

Female general practitioners (GPs) have higher chlamydia testing rates than male GPs, yet it is unclear whether this is due to lack of knowledge among male GPs or because female GPs consult and test more female patients

Mathematics difficulties in extremely preterm children : evidence of a specific deficit in basic mathematics processing

Background: Extremely preterm (EP, <26 wk gestation) children have been observed to have poor academic achievement in comparison to their term-born peers, especially in mathematics. This study investigated potential underlying causes of this difficulty. Methods: A total of 219 EP participants were compared with 153 term-born control children at 11 y of age. All children were assessed by a psychologist on a battery of standardized cognitive tests and a number estimation test assessing children’s numerical representations. Results: EP children underperformed in all tests in comparison with the term controls (the majority of Ps < 0.001). Different underlying relationships between performance on the number estimation test and mathematical achievement were found in EP as compared with control children. That is, even after controlling for cognitive ability, a relationship between number representations and mathematical performance persisted for EP children only (EP: r = 0.346, n = 186, P < 0.001; control: r = 0.095, n = 146, P = 0.256). Conclusion: Interventions for EP children may target improving children’s numerical representations in order to subsequently remediate their mathematical skills

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Parents and Teachers Make Different Contributions to a Shared Perspective on Hyperactive–Impulsive and Inattentive Symptoms: A Multivariate Analysis of Parent and Teacher Ratings on the Symptom Domains of ADHD

Attention deficit hyperactivity disorder (ADHD) is characterised by developmentally inappropriate and impairing levels of inattentive and hyperactive–impulsive behaviours. We aimed to investigate the differential effects of parent and teacher ratings on inattention and hyperactivity–impulsivity and the extent of genetic overlap between the two behavioural dimensions. Multivariate structural equation modelling was performed on DSM-IV based ADHD ratings by parents and teachers collected on a general population sample of 672 twin pairs, at ages 7–10 years. This study is the first to simultaneously use parent and teacher ratings in twin modelling to examine the effects of different raters on the two behavioural dimensions of ADHD. The findings indicated that hyperactivity–impulsivity and inattention load on to separate latent factors that represent a common behavioural view for both parents and teachers, although there are additional aspects to the observations of these behaviours that are unique to each type of rater. The findings further indicate some shared aetiology for hyperactivity–impulsivity and inattention as measured by both parent and teacher ratings, in agreement with previous findings on the aetiology of the two symptom dimensions of ADHD

Negotiating the transition from adolescence to motherhood: Coping with prenatal and parenting stress in teenage mothers in Mulago hospital, Uganda

<p>Abstract</p> <p>Background</p> <p>Adolescence is a transitional stage from childhood to adulthood that is characterized by physical, physiological, psychosocial and behavioral changes that are influenced to a large extent by the age, culture and socialization of the individual. To explore what adolescent mothers perceive as their struggles during the period of transition from childhood to parenthood (through motherhood) and to describe strategies employed in coping with stress of pregnancy, motherhood and parenthood.</p> <p>Methods</p> <p>Longitudinal qualitative study involving twenty two in-depth interviews and six focus group discussions among pregnant adolescents who were followed from pregnant to delivery, from January 2004 to August 2005. Participant were selected by theoretical sampling and data was analyzed using grounded theory.</p> <p>Results</p> <p>Overall, young adolescents reported more anxiety, loss of self esteem (when they conceived), difficulty in accessing financial, moral and material support from parents or partners and stigmatization by health workers when they sought care from health facilities. Three strategies by which adolescent mothers cope with parenting and pregnancy stress that were described as utilizing opportunities (thriving), accommodating the challenges (bargaining and surviving), or failure (despairing), and varied in the extent to which they enabled adolescents to cope with the stress.</p> <p>Conclusion</p> <p>Adolescents on the transition to motherhood have variable needs and aspirations and utilize different strategies to cope with the stress of pregnancy and parenthood.</p

Machine learning for comprehensive forecasting of Alzheimer's Disease progression

Most approaches to machine learning from electronic health data can only predict a single endpoint. The ability to simultaneously simulate dozens of patient characteristics is a crucial step towards personalized medicine for Alzheimer’s Disease. Here, we use an unsupervised machine learning model called a Conditional Restricted Boltzmann Machine (CRBM) to simulate detailed patient trajectories. We use data comprising 18-month trajectories of 44 clinical variables from 1909 patients with Mild Cognitive Impairment or Alzheimer’s Disease to train a model for personalized forecasting of disease progression. We simulate synthetic patient data including the evolution of each sub-component of cognitive exams, laboratory tests, and their associations with baseline clinical characteristics. Synthetic patient data generated by the CRBM accurately reflect the means, standard deviations, and correlations of each variable over time to the extent that synthetic data cannot be distinguished from actual data by a logistic regression. Moreover, our unsupervised model predicts changes in total ADAS-Cog scores with the same accuracy as specifically trained supervised models, additionally capturing the correlation structure in the components of ADAS-Cog, and identifies sub-components associated with word recall as predictive of progression

Social-Skills and Parental Training plus Standard Treatment versus Standard Treatment for Children with ADHD – The Randomised SOSTRA Trial

To investigate the effects of social-skills training and parental training programme for children with attention deficit hyperactivity disorder (ADHD).We conducted a randomized two-armed, parallel group, assessor-blinded superiority trial consisting of social-skills training plus parental training and standard treatment versus standard treatment alone. A sample size calculation showed at least 52 children should be included for the trial with follow up three and six months after randomization. The primary outcome measure was ADHD symptoms and secondary outcomes were social skills and emotional competences. RESULTS 56: children (39 boys, 17 girls, mean age 10.4 years, SD 1.31) with ADHD were randomized, 28 to the experimental group and 27 to the control group. Mixed-model analyses with repeated measures showed that the time course (y  =  a + bt + ct(2)) of ADHD symptoms (p = 0.40), social skills (p = 0.80), and emotional competences (p = 0.14) were not significantly influenced by the intervention.Social skills training plus parental training did not show any significant benefit for children with attention deficit hyperactivity disorder when compared with standard treatment. More and larger randomized trials are needed.ClinicalTrials.gov NCT00937469