Spectroscopy of z ∼ 6 i-dropout galaxies : frequency of Lyα emission and the sizes of Lyα-emitting galaxies

We report on deep spectroscopy, using LRIS on Keck I and FORS2 on the VLT, of a sample of 22 candidate z similar to 6 Lyman break galaxies (LBGs) selected by the (i)775 - z(850) > 1: 3 dropout criterion. Redshifts could be measured for eight objects. These redshifts are all in the range z = 5: 5-6.1, confirming the efficiency of the i775 - z850 color selection technique. Six of the confirmed galaxies show Ly alpha emission. Assuming that the 14 objects without redshifts are z similar to 6 LBGs that lack detectable Ly alpha emission lines, we infer that the fraction of Ly alpha-emitting LBGs with Ly alpha equivalent widths greater than 20 angstrom among z similar to 6 LBGs is approximate to 30%, similar to that found at z similar to 3. Every Ly alpha-emitting object in our sample is compact, with half-light radii r(hl) 97% confidence. We speculate that the small sizes of the Ly alpha-emitting LBGs are due to these objects being less massive than other LBGs at z similar to 6

A candidate redshift z ~ 10 galaxy and rapid changes in that population at an age of 500 Myr

Searches for very-high-redshift galaxies over the past decade have yielded a large sample of more than 6,000 galaxies existing just 900-2,000 million years (Myr) after the Big Bang (redshifts 6 > z > 3; ref. 1). The Hubble Ultra Deep Field (HUDF09) data have yielded the first reliable detections of z ~ 8 galaxies that, together with reports of a gamma-ray burst at z ~ 8.2 (refs 10, 11), constitute the earliest objects reliably reported to date. Observations of z ~ 7-8 galaxies suggest substantial star formation at z > 9-10. Here we use the full two-year HUDF09 data to conduct an ultra-deep search for z ~ 10 galaxies in the heart of the reionization epoch, only 500 Myr after the Big Bang. Not only do we find one possible z ~ 10 galaxy candidate, but we show that, regardless of source detections, the star formation rate density is much smaller (~10%) at this time than it is just ~200 Myr later at z ~ 8. This demonstrates how rapid galaxy build-up was at z ~ 10, as galaxies increased in both luminosity density and volume density from z ~ 8 to z ~ 10. The 100-200 Myr before z ~ 10 is clearly a crucial phase in the assembly of the earliest galaxies.Comment: 41 pages, 14 figures, 2 tables, Nature, in pres

Stemming the Tide of Antibiotic Resistance (STAR): A protocol for a trial of a complex intervention addressing the 'why' and 'how' of appropriate antibiotic prescribing in general practice

BACKGROUND: After some years of a downward trend, antibiotic prescribing rates in the community have tended to level out in many countries. There is also wide variation in antibiotic prescribing between general practices, and between countries. There are still considerable further gains that could be made in reducing inappropriate antibiotic prescribing, but complex interventions are required. Studies to date have generally evaluated the effect of interventions on antibiotic prescribing in a single consultation and pragmatic evaluations that assess maintenance of new skills are rare. This paper describes the protocol for a pragmatic, randomized evaluation of a complex intervention aimed at reducing antibiotic prescribing by primary care clinicians. METHODS AND DESIGN: We developed a Social Learning Theory based, blended learning program (on-line learning, a practice based seminar, and context bound learning) called the STAR Educational Program. The 'why of change' is addressed by providing clinicians in general practice with information on antibiotic resistance in urine samples submitted by their practice and their antibiotic prescribing data, and facilitating a practice-based seminar on the implications of this data. The 'how of change' is addressed through context-bound communication skills training and information on antibiotic indication and choice. This intervention will be evaluated in a trial involving 60 general practices, with general practice as the unit of randomization (clinicians from each practice to either receive the STAR Educational Program or not) and analysis. The primary outcome will be the number of antibiotic items dispensed over one year. An economic and process evaluation will also be conducted. DISCUSSION: This trial will be the first to evaluate the effectiveness of this type of theory-based, blended learning intervention aimed at reducing antibiotic prescribing by primary care clinicians. Novel aspects include feedback of practice level data on antimicrobial resistance and prescribing, use of principles from motivational interviewing, training in enhanced communication skills that incorporates context-bound experience and reflection, and using antibiotic dispensing over one year (as opposed to antibiotic prescribing in a single consultation) as the main outcome

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer

As breast volume may be associated with heart cancer risk, we studied the relationship between breast volume, CYP1A2*1F and coffee intake. Among healthy premenopausal non-hormone users, 3+ cups per day was associated with lower volume only in C-allele carriers (Pinteraction=0.02), which is consistent with reports that coffee protects only C-allele carriers against breast cancer

Lack of awareness of erectile dysfunction in many men with risk factors for erectile dysfunction

<p>Abstract</p> <p>Background</p> <p>Men with erectile dysfunction often have concurrent medical conditions. Conversely, men with these conditions may also have underlying erectile dysfunction. The prevalence of unrecognized erectile dysfunction in men with comorbidities commonly associated with erectile dysfunction was determined in men invited to participate in a double-blind, randomized, placebo-controlled trial of sildenafil citrate.</p> <p>Methods</p> <p>Men ≥30 years old presenting with ≥1 erectile dysfunction risk factor (controlled hypertension, hypercholesterolemia, smoking, metabolic syndrome, stable coronary artery disease, diabetes, depression, lower urinary tract symptoms, obesity [body mass index ≥30 kg/m²] or waist circumference ≥40 inches), and not previously diagnosed with erectile dysfunction were evaluated. The screening question, "Do you have erectile dysfunction?," with responses of "no," "yes," and "unsure," and the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) were administered.</p> <p>Results</p> <p>Of 1084 men screened, 1053 answered the screening question and also had IIEF-EF scores. IIEF-EF scores indicating erectile dysfunction occurred in 71% (744/1053), of whom 54% (399/744) had moderate or severe erectile dysfunction. Of 139 answering "yes," 526 answering "unsure," and 388 answering "no," 96%, 90%, and 36%, respectively, had some degree of erectile dysfunction. The mean±SD (range) number of risk factors was 2.9 ± 1.7 (3-8) in the "yes" group, 3.2 ± 1.7 (3-9) in the "unsure" group, and 2.6 ± 1.5 (2-8) in the "no" group.</p> <p>Conclusion</p> <p>Although awareness of having erectile dysfunction was low, most men with risk factors had IIEF-EF scores indicating erectile dysfunction. Erectile dysfunction should be suspected and assessed in men with risk factors, regardless of their apparent level of awareness of erectile dysfunction.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier NCT00343200.</p

A biophysical model of endocannabinoid-mediated short term depression in hippocampal inhibition

Memories are believed to be represented in the synaptic pathways of vastly interconnected networks of neurons. The plasticity of synapses, that is, their strengthening and weakening depending on neuronal activity, is believed to be the basis of learning and establishing memories. An increasing number of studies indicate that endocannabinoids have a widespread action on brain function through modulation of synap–tic transmission and plasticity. Recent experimental studies have characterised the role of endocannabinoids in mediating both short- and long-term synaptic plasticity in various brain regions including the hippocampus, a brain region strongly associated with cognitive functions, such as learning and memory. Here, we present a biophysically plausible model of cannabinoid retrograde signalling at the synaptic level and investigate how this signalling mediates depolarisation induced suppression of inhibition (DSI), a prominent form of shortterm synaptic depression in inhibitory transmission in hippocampus. The model successfully captures many of the key characteristics of DSI in the hippocampus, as observed experimentally, with a minimal yet sufficient mathematical description of the major signalling molecules and cascades involved. More specifically, this model serves as a framework to test hypotheses on the factors determining the variability of DSI and investigate under which conditions it can be evoked. The model reveals the frequency and duration bands in which the post-synaptic cell can be sufficiently stimulated to elicit DSI. Moreover, the model provides key insights on how the state of the inhibitory cell modulates DSI according to its firing rate and relative timing to the post-synaptic activation. Thus, it provides concrete suggestions to further investigate experimentally how DSI modulates and is modulated by neuronal activity in the brain. Importantly, this model serves as a stepping stone for future deciphering of the role of endocannabinoids in synaptic transmission as a feedback mechanism both at synaptic and network level

Assaying Total Carotenoids in Flours of Corn and Sweetpotato by Laser Photoacoustic Spectroscopy

This study describes the application of the laser photoacoustic spectroscopy (PAS) for quantification of total carotenoids (TC) in corn flours and sweetpotato flours. Overall, thirty-three different corn flours and nine sweetpotato flours were investigated. All PAS measurements were performed at room temperature using 488-nm argon laser radiation for excitation and mechanical modulation of 9 and 30 Hz. The measurements were repeated within a run and within several days or months. The UV–Vis spectrophotometry was used as the reference method. The concentration range that allows for the reliable analysis of TC spans a region from 1 to 40 mg kg−1 for corn flours and from 9 to 40 mg kg−1 for sweetpotato flours. In the case of sweetpotato flours, the quantification may extend even to 240 mg kg−1 TC. The estimated detection limit values for TC in corn and sweetpotato flours were 0.1 and 0.3 mg kg−1, respectively. The computed repeatability (n = 3–12) and intermediate precision (n = 6–28) RSD values at 9 and 30 Hz are comparable: 0.1–17.1% and 5.3–14.7% for corn flours as compared with 1.4–9.1% and 4.2–23.0% for sweetpotato flours. Our results show that PAS can be successfully used as a new analytical tool to simply and rapidly screen the flours for their nutritional potential based on the total carotenoid concentration

Stochastically Gating Ion Channels Enable Patterned Spike Firing through Activity-Dependent Modulation of Spike Probability

The transformation of synaptic input into patterns of spike output is a fundamental operation that is determined by the particular complement of ion channels that a neuron expresses. Although it is well established that individual ion channel proteins make stochastic transitions between conducting and non-conducting states, most models of synaptic integration are deterministic, and relatively little is known about the functional consequences of interactions between stochastically gating ion channels. Here, we show that a model of stellate neurons from layer II of the medial entorhinal cortex implemented with either stochastic or deterministically gating ion channels can reproduce the resting membrane properties of stellate neurons, but only the stochastic version of the model can fully account for perithreshold membrane potential fluctuations and clustered patterns of spike output that are recorded from stellate neurons during depolarized states. We demonstrate that the stochastic model implements an example of a general mechanism for patterning of neuronal output through activity-dependent changes in the probability of spike firing. Unlike deterministic mechanisms that generate spike patterns through slow changes in the state of model parameters, this general stochastic mechanism does not require retention of information beyond the duration of a single spike and its associated afterhyperpolarization. Instead, clustered patterns of spikes emerge in the stochastic model of stellate neurons as a result of a transient increase in firing probability driven by activation of HCN channels during recovery from the spike afterhyperpolarization. Using this model, we infer conditions in which stochastic ion channel gating may influence firing patterns in vivo and predict consequences of modifications of HCN channel function for in vivo firing patterns

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy