NMDA spikes enhance action potential generation during sensory input

Recent evidence in vitro suggests that the tuft dendrites of pyramidal neurons are capable of evoking local NMDA receptor–dependent electrogenesis, so-called NMDA spikes. However, it has so far proved difficult to demonstrate their existence in vivo. Moreover, it is not clear whether NMDA spikes are relevant to the output of pyramidal neurons. We found that local NMDA spikes occurred in tuft dendrites of layer 2/3 pyramidal neurons both spontaneously and following sensory input, and had a large influence on the number of output action potentials. Using two-photon activation of an intracellular caged NMDA receptor antagonist (tc-MK801), we found that isolated NMDA spikes typically occurred in multiple branches simultaneously and that sensory stimulation substantially increased their probability. Our results demonstrate that NMDA receptors have a vital role in coupling the tuft region of the layer 2/3 pyramidal neuron to the cell body, enhancing the effectiveness of layer 1 input

Spatially resolved spectroscopy of Cassiopeia A with MECS on board BeppoSAX

We have performed the first detailed spatially resolved spectroscopy of Cas A in the 1.6-10 keV energy range, using data taken with the MECS spectrometer on board the BeppoSAX Observatory. We performed a spatial deconvolution of the data and eventually generated a set of spectra, covering a region of about 3 arcmin radius around the centre of Cas A. The results obtained by fitting these spectra using a non-equilibrium ionisation plasma model and a power law, are: (i) a single thermal component is sufficient to fit all the spectra; (ii) kT is rather uniformly distributed with a minimum in the east and a maximum in the west, and no evidence is found for high kT expected from the interaction of the main shock with the ISM; (iii) from the distribution of the values of the ionisation parameter n_et we infer the presence of two distinct components: the first (a) in the range 1-10 cm^(-3), the second (b) with values ten times higher; if we associate component a to the CSM and component b to the ejecta, the mass ratio M(a)/M(b)<= 1/10 indicates a progenitor star that lost only a small fraction of the envelope during its pre-SN life. In this hypothesis the distribution of component b across the remnant suggests that the explosion was not spherically symmetric; (iv) the distribution of abundances indicates that we are detecting a CSM component with almost solar composition, and an ejecta component enriched in heavier elements. Abundances found for alpha-elements are consistent with the current view that Cas A was produced by the explosion of a massive star.Comment: 16 pages, 9 PostScript figures, 4 tables, Accepted for publication on Astronomy & Astrophysics (submitted July 12, 2000; accepted December 20, 2000

WASP-44b, WASP-45b and WASP-46b: three short-period, transiting extrasolar planets

We report the discovery of three extrasolar planets that transit their moderately bright (Vmag = 12-13) host stars. WASP-44b is a 0.89-MJup planet in a 2.42-day orbit around a G8V star. WASP-45b is a 1.03-MJup planet which passes in front of the limb of its K2V host star every 3.13 days. Weak Ca II H+K emission seen in the spectra of WASP-45 suggests the star is chromospherically active. WASP-46b is a 2.10-MJup planet in a 1.43-day orbit around a G6V star. Rotational modulation of the light curves of WASP-46 and weak Ca II H+K emission in its spectra show the star to be photospherically and chromospherically active. We imposed circular orbits in our analyses as the radial velocity data are consistent with (near-)circular orbits, as could be expected from both empirical and tidal-theory perspectives for such short-period, Jupiter-mass planets. We discuss the impact of fitting for eccentric orbits for such planets when not supported by the data. The derived planetary and stellar radii depend on the fitted eccentricity and these parameters inform intense theoretical efforts concerning tidal circularisation and heating, bulk planetary composition and the observed systematic errors in planetary and stellar radii. As such, we recommend exercising caution in fitting the orbits of short period, Jupiter-mass planets with an eccentric model when there is no evidence of non-circularity.Comment: 12 pages, 8 figures, 6 tables. As accepted for publication in MNRA

An evaluation of tuberculosis contact investigations against national standards.

BACKGROUND: Contact tracing is a key element in England's 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed. METHODS: We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London's TB Register, identifying characteristics associated with improved indicators and yield. RESULTS: Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2-6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection. CONCLUSIONS: These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy's success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes

Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London.

BACKGROUND: In January 2016, clinical TB guidance in the UK changed to no longer recommend screening contacts of non-pulmonary, non-laryngeal (ETB) index cases. However, no new evidence was cited for this change, and there is evidence that screening these contacts may be worthwhile. The objective of this study was to estimate the cost-effectiveness of screening contacts of adult ETB cases and adult pulmonary or laryngeal TB (PTB) cases in London, UK. METHODS: We carried out a cross-sectional analysis of data collected on TB index cases and contacts in the London TB register and an economic evaluation using a static model describing contact tracing outcomes. Incremental cost-effectiveness ratios (ICERs) were calculated using no screening as the baseline comparator. All adult TB cases (≥15 years old) in London from 2012 to 2015, and their contacts, were eligible (2465/5084 PTB and 2559/6090 ETB index cases were included). RESULTS: Assuming each contact with PTB infects one person/month, the ICER of screening contacts of ETB cases was £78 000/quality-adjusted life-years (QALY) (95% CI 39 000 to 140 000), and screening contacts of PTB cases was £30 000/QALY (95% CI 18 000 to 50 000). The ICER of screening contacts of ETB cases was £30 000/QALY if each contact with PTB infects 3.4 people/month. Limitations of this study include the use of self-reported symptomatic periods and lack of knowledge about onward transmission from PTB contacts. CONCLUSIONS: Screening contacts of ETB cases in London was almost certainly not cost-effective at any conventional willingness-to-pay threshold in England, supporting recent changes to National Institute for Health and Care Excellence national guidelines

Pulmonary Mycobacterium avium-intracellulare is the main driver of the rise in non-tuberculous mycobacteria incidence in England, Wales and Northern Ireland, 2007–2012

BACKGROUND: The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level. METHODS: All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included. RESULTS: Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001). The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old. CONCLUSION: Using a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change. We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required

A Multi-Wavelength Study of Parent Volatile Abundances in Comet C/2006 M4 (SWAN)

Volatile organic emissions were detected post-perihelion in the long period comet C/2006 M4 (SWAN) in October and November 2006. Our study combines target-of-opportunity, observations using the infrared Cryogenic Echelle Spectrometer (CSHELL) at the NASA-IRTF 3-m telescope, and millimeter wavelength observations using the Arizona Radio Observatory (ARO) 12-m telescope. Five parent volatiles were measured with CSHELL (H2O, CO, CH3OH, CH4, and C2H6), and two additional species (HCN and CS) were measured with the ARID 12-m. These revealed highly depleted CO and somewhat enriched CH3OH compared with abundances observed in the dominant group of long-period (Oort cloud) comets in our sample and similar to those observed recently in Comet 8P/Tuttle. This may indicate highly efficient H-atom addition to CO at very low temperature (approx.10-20 K) on the surfaces of interstellar (pre-cometary) grains. Comet C12006 M4 had nearly "normal" C2H6, and CH4, suggesting a processing history similar to that experienced by the dominant group. When compared with estimated water production at the time of the millimeter observations, HCN was slightly depleted compared with the normal abundance in comets based on 1R observations but was consistent with the majority of values from the millimeter. The ratio CS/HCN in C/2006 M4 was within the range measured in ten comets at millimeter wavelengths. The higher apparent H-atom conversion efficiency compared with most comets may indicate that the icy grains incorporated into C/2006 M4 were exposed to higher H-atom densities, or alternatively to similar densities but for a longer period of time

WASP-31b: a low-density planet transiting a metal-poor, late-F-type dwarf star

We report the discovery of the low-density, transiting giant planet WASP-31b. The planet is 0.48 Jupiter masses and 1.55 Jupiter radii. It is in a 3.4-day orbit around a metal-poor, late-F-type, V = 11.7 dwarf star, which is a member of a common proper motion pair. In terms of its low density, WASP-31b is second only to WASP-17b, which is a more highly irradiated planet of similar mass.Comment: 6 pages, 5 figures, 4 tables. As accepted for publication in A&A; bibcode = 2011A&A...531A..60

Tracking a northern fulmar from a Scottish nesting site to the Charlie-Gibbs Fracture Zone : Evidence of linkage between coastal breeding seabirds and Mid-Atlantic Ridge feeding sites

Peer reviewedPublisher PD