Saturated gain spectrum of VECSELs determined by transient measurement of lasing onset

We describe time-resolved measurements of the evolution of the spectrum of radiation emitted by an optically-pumped continuous-wave InGaAs-GaAs quantum well laser, recorded as lasing builds up from noise to steady state. We extract a fitting parameter corresponding to the gain dispersion of the parabolic spectrum equal to ?79 ± 30 fs2 and ?36 ± 6 fs2 for a resonant and anti-resonant structure, respectively. Furthermore the recorded evolution of the spectrum allows for the calculation of an effective FWHM gain bandwidth for each structure, of 11 nm and 18 nm, respectively

Assessment of culture and environment in the Adolescent Brain and Cognitive Development Study: Rationale, description of measures, and early data.

Neurodevelopmental maturation takes place in a social environment in addition to a neurobiological one. Characterization of social environmental factors that influence this process is therefore an essential component in developing an accurate model of adolescent brain and neurocognitive development, as well as susceptibility to change with the use of marijuana and other drugs. The creation of the Culture and Environment (CE) measurement component of the ABCD protocol was guided by this understanding. Three areas were identified by the CE Work Group as central to this process: influences relating to CE Group membership, influences created by the proximal social environment, influences stemming from social interactions. Eleven measures assess these influences, and by time of publication, will have been administered to well over 7,000 9-10 year-old children and one of their parents. Our report presents baseline data on psychometric characteristics (mean, standard deviation, range, skewness, coefficient alpha) of all measures within the battery. Effectiveness of the battery in differentiating 9-10 year olds who were classified as at higher and lower risk for marijuana use in adolescence was also evaluated. Psychometric characteristics on all measures were good to excellent; higher vs. lower risk contrasts were significant in areas where risk differentiation would be anticipated

Natriuretic Peptides and Nitric Oxide Stimulate cGMP Synthesis in Different Cellular Compartments

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the particulate guanylyl cyclase and the nitric oxide donor S-nitroso-n-acetylpenicillamine (SNAP) was used to activate the soluble guanylyl cyclase. CNG channel activity was monitored by measuring Ca2+ or Mn2+ influx through the channels using the fluorescent dye, fura-2. We found that in HEK-NPRA cells, ANP-induced increases in cGMP levels activated CNG channels in a dose-dependent manner (0.05–10 nM), whereas SNAP (0.01–100 μM) induced increases in cGMP levels triggered little or no activation of CNG channels (P < 0.01). After pretreatment with 100 μM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase inhibitor, ANP-induced Mn2+ influx through CNG channels was significantly enhanced, while SNAP-induced Mn2+ influx remained small. In contrast, we found that in the presence of IBMX, both 1 nM ANP and 100 μM SNAP triggered similar increases in total cGMP levels. We next sought to determine if cGMP signals are compartmentalized in VSMCs, which endogenously express particulate and soluble guanylyl cyclase. We found that 10 nM ANP induced activation of CNG channels more readily than 100 μM SNAP; whereas 100 μM SNAP triggered higher levels of total cellular cGMP accumulation. These results suggest that cGMP signals are spatially segregated within cells, and that the functional compartmentalization of cGMP signals may underlie the unique actions of ANP and nitric oxide

Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10−8), including rs12700667 on 7p15.2 (P = 1.6 × 10−9), rs7521902 near WNT4 (P = 1.8 × 10−15), rs10859871 near VEZT (P = 4.7 × 10−15), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10−8), rs7739264 near ID4 (P = 6.2 × 10−10) and rs13394619 in GREB1 (P = 4.5 × 10−8). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10−8) and rs4141819 on 2p14 (P = 9.2 × 10−8). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways

Longitudinal decline in structural networks predicts dementia in cerebral small vessel disease.

OBJECTIVE: To determine whether longitudinal change in white matter structural network integrity predicts dementia and future cognitive decline in cerebral small vessel disease (SVD). To investigate whether network disruption has a causal role in cognitive decline and mediates the association between conventional MRI markers of SVD with both cognitive decline and dementia. METHODS: In the prospective longitudinal SCANS (St George's Cognition and Neuroimaging in Stroke) Study, 97 dementia-free individuals with symptomatic lacunar stroke were followed with annual MRI for 3 years and annual cognitive assessment for 5 years. Conversion to dementia was recorded. Structural networks were constructed from diffusion tractography using a longitudinal registration pipeline, and network global efficiency was calculated. Linear mixed-effects regression was used to assess change over time. RESULTS: Seventeen individuals (17.5%) converted to dementia, and significant decline in global cognition occurred (p = 0.0016). Structural network measures declined over the 3-year MRI follow-up, but the degree of change varied markedly between individuals. The degree of reductions in network global efficiency was associated with conversion to dementia (B = -2.35, odds ratio = 0.095, p = 0.00056). Change in network global efficiency mediated much of the association of conventional MRI markers of SVD with cognitive decline and progression to dementia. CONCLUSIONS: Network disruption has a central role in the pathogenesis of cognitive decline and dementia in SVD. It may be a useful disease marker to identify that subgroup of patients with SVD who progress to dementia

The difference that tenure makes

This paper argues that housing tenures cannot be reduced to either production relations or consumption relations. Instead, they need to be understood as modes of housing distribution, and as having complex and dynamic relations with social classes. Building on a critique of both the productionist and the consumptionist literature, as well as of formalist accounts of the relations between tenure and class, the paper attempts to lay the foundations for a new theory of housing tenure. In order to do this, a new theory of class is articulated, which is then used to throw new light on the nature of class-tenure relations

NGC 7582: The Prototype Narrow-Line X-ray Galaxy

NGC 7582 is a candidate prototype of the Narrow Line X-ray Galaxies (NLXGs) found in deep X-ray surveys. An ASCA observation shows the hard (> 3 keV) X-ray continuum of NGC 7582 drops 40% in ~6 ks, implying an AGN, while the soft band (< 3 keV) does not drop in concert with the hard continuum, requiring a separate component. The X-ray spectrum of NGC 7582 also shows a clear 0.5-2 keV soft (kT = 0.8 (+0.9,-0.3) keV or Gamma = 2.4 +/- 0.6; L(X) = 6 x 10**40 ergs s**-1) low--energy component, in addition to a heavily absorbed [N(H) = (6 +/- 2)\times 10**22 cm**-2 ] and variable 2-10 keV power law [Gamma = 0.7 (+0.3,-0.4); L(X) = (1.7-2.3) x 10**42 ergs s**-1]. This is one of the flattest 2-10 keV slopes in any AGN observed with ASCA. (The ROSAT HRI image of NGC 7582 further suggests extent to the SE.) These observations make it clear that the hard X-ray emission of NGC 7582, the most "narrow-line" of the NLXGs, is associated with an AGN. The strong suggestion is that all NLXGs are obscured AGNs, as hypothesized to explain the X-ray background spectral paradox. The separate soft X-ray component makes NGC 7582 (and by extension other NLXGs) detectable as a ROSAT source.Comment: text: Latex2e 10 pages, including 1 table, and 2 postscript figures via psfi

A national survey of the diagnosis and management of suspected ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) affects up to 20% of patients admitted to intensive care units (ICU). It is associated with increased morbidity, mortality and healthcare costs. Despite published guidelines, variability in diagnosis and management exists, the extent of which remains unclear. We sought to characterise consultant opinions surrounding diagnostic and management practice for VAP in the UK. METHODS: An online survey was sent to all consultant members of the UK Intensive Care Society (n=∼1500). Data were collected regarding respondents' individual practice in the investigation and management of suspected VAP including use of diagnostic criteria, microbiological sampling, chest X-ray (CXR), bronchoscopy and antibiotic treatments. RESULTS: 339 (23%) responses were received from a broadly representative spectrum of ICU consultants. All respondents indicated that microbiological confirmation should be sought, the majority (57.8%) stating they would take an endotracheal aspirate prior to starting empirical antibiotics. Microbiology reporting services were described as qualitative only by 29.7%. Only 17% of respondents had access to routine reporting of CXRs by a radiologist. Little consensus exists regarding technique for bronchoalveolar lavage (BAL) with the reported volume of saline used ranging from 5 to 500 mL. 24.5% of consultants felt inadequately trained in bronchoscopy. CONCLUSIONS: There is wide variability in the approach to diagnosis and management of VAP among UK consultants. Such variability challenges the reliability of the diagnosis of VAP and its reported incidence as a performance indicator in healthcare systems. The data presented suggest increased radiological and microbiological support, and standardisation of BAL technique, might improve this situation