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Leishmania amazonensis is a protozoan that primarily causes cutaneous leishmaniasis in humans. The parasite relies on the amino acid arginine to survive within macrophages and establish infection, since it is a precursor for producing polyamines. On the other hand, arginine can be metabolized via nitric oxide synthase 2 (NOS2) to produce the microbicidal molecule nitric oxide (NO), although this mechanism does not apply to human macrophages since they lack NOS2 activity. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at posttranscriptional levels. Our previous work showed that mmu-miR-294 targets Nos2 favoring Leishmania survival in murine macrophages. Here, we demonstrate that human macrophages upregulate the hsa-miR-372, hsa-miR-373, and hsa-miR-520d, which present the same seed sequence as the murine mmu-miR-294. Inhibition of the miR-372 impaired Leishmania survival in THP-1 macrophages and the effect was further enhanced with combinatorial inhibition of the miR-372/373/520d family, pointing to a cooperative mechanism. However, this reduction in survival is not caused by miRNA-targeting of NOS2, since the seed-binding motif found in mice is not conserved in the human 3′UTR. Instead, we showed the miR-372/373/520d family targeting the macrophage's main arginine transporter SLC7A2/CAT2 during infection. Arginine-related metabolism was markedly altered in response to infection and miRNA inhibition, as measured by Mass Spectrometry-based metabolomics. We found that Leishmania infection upregulates polyamines production in macrophages, as opposed to simultaneous inhibition of miR-372/373/520d, which decreased putrescine and spermine levels compared to the negative control. Overall, our study demonstrates miRNA-dependent modulation of polyamines production, establishing permissive conditions for intracellular parasite survival. Although the effector mechanisms causing host cell immunometabolic adaptations involve various parasite and host-derived signals, our findings suggest that the miR-372/373/520d family may represent a potential target for the development of new therapeutic strategies against cutaneous leishmaniasis. [ABSTRACT FROM AUTHOR]

Aims: Plectin, a universally expressed multi‐functional cytolinker protein, is crucial for intermediate filament networking, including crosstalk with actomyosin and microtubules. In addition to its involvement in a number of diseases affecting skin, skeletal muscle, heart, and other stress‐exposed tissues, indications for a neuropathological role of plectin have emerged. Having identified P1c as the major isoform expressed in neural tissues in previous studies, our aim for the present work was to investigate whether, and by which mechanism(s), the targeted deletion of this isoform affects neuritogenesis and proper nerve cell functioning. Methods: For ex vivo phenotyping, we used dorsal root ganglion and hippocampal neurons derived from isoform P1c‐deficient and plectin‐null mice, complemented by in vitro experiments using purified proteins and cell fractions. To assess the physiological significance of the phenotypic alterations observed in P1c‐deficient neurons, P1c‐deficient and wild‐type littermate mice were subjected to standard behavioural tests. Results: We demonstrate that P1c affects axonal microtubule dynamics by isoform‐specific interaction with tubulin. P1c deficiency in neurons leads to altered dynamics of microtubules and excessive association with tau protein, affecting neuritogenesis, neurite branching, growth cone morphology, and translocation and directionality of movement of vesicles and mitochondria. On the organismal level, we found P1c deficiency manifesting as impaired pain sensitivity, diminished learning capabilities and reduced long‐term memory of mice. Conclusions: Revealing a regulatory role of plectin scaffolds in microtubule‐dependent nerve cell functions, our results have potential implications for cytoskeleton‐related neuropathies. [ABSTRACT FROM AUTHOR]

Using high magnetic fields up to 60 T, we report magneto-transport and photoluminescence (PL) studies of a two-dimensional electron gas (2DEG) in a GaN/AlGaN heterojunction grown by molecular-beam epitaxy. Transport measurements demonstrate that the quantum limit can be exceeded (Landau level filling factor ν < 1) and show evidence for the ν = 2 / 3 fractional quantum Hall state. Simultaneous optical and transport measurements reveal synchronous quantum oscillations of both the PL intensity and the longitudinal resistivity in the integer quantum Hall regime. PL spectra directly reveal the dispersion of occupied Landau levels in the 2DEG and, therefore, the electron mass. These results demonstrate the utility of high (pulsed) magnetic fields for detailed measurements of quantum phenomena in high-density 2DEGs. [ABSTRACT FROM AUTHOR]

Aims: We investigated newly generated immortalized heterozygous and homozygous R349P desmin knock‐in myoblasts in conjunction with the corresponding desminopathy mice as models for desminopathies to analyse major protein quality control processes in response to the presence of R349P mutant desmin. Methods: We used hetero‐ and homozygous R349P desmin knock‐in mice for analyses and for crossbreeding with p53 knock‐out mice to generate immortalized R349P desmin knock‐in skeletal muscle myoblasts and myotubes. Skeletal muscle sections and cultured muscle cells were investigated by indirect immunofluorescence microscopy, proteasomal activity measurements and immunoblotting addressing autophagy rate, chaperone‐assisted selective autophagy and heat shock protein levels. Muscle sections were further analysed by transmission and immunogold electron microscopy. Results: We demonstrate that mutant desmin (i) increases proteasomal activity, (ii) stimulates macroautophagy, (iii) dysregulates the chaperone assisted selective autophagy and (iv) elevates the protein levels of αB‐crystallin and Hsp27. Both αB‐crystallin and Hsp27 as well as Hsp90 displayed translocation patterns from Z‐discs as well as Z‐I junctions, respectively, to the level of sarcomeric I‐bands in dominant and recessive desminopathies. Conclusions: Our findings demonstrate that the presence of R349P mutant desmin causes a general imbalance in skeletal muscle protein homeostasis via aberrant activity of all major protein quality control systems. The augmented activity of these systems and the subcellular shift of essential heat shock proteins may deleteriously contribute to the previously observed increased turnover of desmin itself and desmin‐binding partners, which triggers progressive dysfunction of the extrasarcomeric cytoskeleton and the myofibrillar apparatus in the course of the development of desminopathies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Simulation is widely used in graduate medical education. A prior survey showed that 80% of Neonatal-Perinatal Medicine (NPM) fellowship programs in the U.S. use simulation. There are multiple ways to provide simulation-based education. One such method is through intensive simulation-based education sessions held at the beginning of a training program, common called 'boot camps'. The aim of this study was to describe the use of simulation-based boot camps in NPM fellowship programs. METHODS: Survey study of Accreditation Council for Graduate Medical Education (ACGME) accredited NPM fellowships in the U.S. RESULTS: Fifty-nine of 98 programs (60%) responded. Thirty six (61%) participated in 1st year fellow boot camps, which focused on procedural skills and newborn resuscitation. Nearly half of programs participated in regional boot camps. Most boot camps were one or two days long. Eleven programs (19%) held 2nd or 3rd year fellow boot camps, which focused on advanced resuscitation and communication. Barriers included lack of faculty protected time (57%), funding (39%), and lack of faculty experience (31%). CONCLUSIONS: A majority of ACGME accredited NPM fellowships participate in 1st year fellows' boot camps. Many participate in regional boot camps. A few programs have 2nd or 3rd year fellow boot camps. Lack of time, funding, and faculty experience were common barriers. [ABSTRACT FROM AUTHOR]

The newly revised sunspot-number series allows for placing historical geoeffective storms in the context of several hundred years of solar activity. Using statistical analyses of the Geostationary Operational Environmental Satellites (GOES) X-ray observations from the past ${\approx}\,30$ years and the Solar and Heliospheric Observatory (SOHO) Large Angle and Spectrometric Coronagraph (LASCO) Coronal Mass Ejection (CME) catalog (1996 - present), we present sunspot-number-dependent flare and CME rates. In particular, we present X-ray flare rates as a function of sunspot number for the past three cycles. We also show that the 1 - 8 Å X-ray background flux is strongly correlated with sunspot number across solar cycles. Similarly, we show that the CME properties ( e.g. proxies related to the CME linear speed and width) are also correlated with sunspot number for Solar Cycles 23 and 24. These updated rates will enable future predictions for geoeffective events and place historical storms in the context of present solar activity. [ABSTRACT FROM AUTHOR]

We have used XMM-Newton's Optical Monitor (OM) images to study the local environment of a sample of 27 ultraluminous X-ray sources (ULXs) in nearby galaxies. UVW1 fluxes were extracted from 100 pc regions centered on the ULX positions. We find that at least 4 ULXs (out of 10 published) have spectral types that are consistent with previous literature values. In addition, the colors are similar to those of young stars. For the highest-luminosity ULXs, the UVW1 fluxes may have an important contribution from the accretion disk. We find that the majority of ULXs are associated with recent star formation. Many of the ULXs in our sample are located inside young OB associations or star-forming regions (SFRs). Based on their colors, we estimated ages and masses for SFRs located within 1 kpc from the ULXs in our sample. The resolution of the OM was insufficient to detect young dense superclusters, but some of these SFRs are massive enough to contain such clusters. Only three ULXs have no associated SFRs younger than ∼50 Myr. The age and mass estimates for clusters were used to test runaway scenarios. The data are, in general, compatible with stellar-mass binaries accreting at super-Eddington rates and ejected by natal kicks. We also tested the hypothesis that ULXs are sub-Eddington accreting intermediate mass black holes ejected by three-body interactions; however, this is not supported well by the data. [ABSTRACT FROM AUTHOR]

An inductive method is used to follow the magnetic-field-dependent susceptibility of the coupled charge density wave (CDW) and spin-Peierls (SP) ordered state behavior in the dual-chain organic conductor perylene2[Pt(mnt)2]. In addition to the coexisting SP-CDW state phase below 8 K and 20 T, the measurements show that a second spin-gapped phase appears above 20 T that coincides with a field-induced insulating phase. The results support a strong coupling of the CDW and SP order parameters even in high magnetic fields, and provide new insight into the nature of the magnetic susceptibility of dual-chain spin and charge systems. [ABSTRACT FROM AUTHOR]

The effective Eddington limit for dusty gas surrounding active galactic nucleus (AGN) is lower than the canonical Eddington limit for hydrogen gas. Previous results from the Swift/Burst Alert Telescope 9-month catalogue suggested that in the overwhelming majority of local AGN, the dusty absorbing gas is below this effective Eddington limit, implying that radiation pressure is insufficient to blow away the absorbing clouds. We present an analysis of three objects from that sample which were found to be close to the effective Eddington limit (NGC 454, 2MASX J03565655−4041453 and XSS J05054−2348), using newly obtained XMM–Newton data. We use the X-ray data to better constrain the absorbing column density, and supplement them with XMM Optical Monitor data, infrared Spitzer and Herschel data were available to construct a broad-band spectral energy distribution to estimate refined bolometric luminosities and Eddington ratios for these three objects. The new XMM–Newton observations show all three objects moving away from the region expected for short-lived absorption in the NH–λEdd plane into the ‘long-lived absorption’ region. We find our conclusions robust to different methods for estimating the bolometric luminosity and Eddington ratio. Interestingly, 2MASX J03565655−4041453 and XSS J05054−2348 now exhibit complex X-ray spectra, at variance with previous analyses of their Swift/X-Ray Telescope data. We find evidence for absorption variability in NGC 454 and 2MASX J03565655−4041453, perhaps implying that although the radiation pressure from the central engine is insufficient to cause clearly detectable outflows, it may cause absorption variations over longer time-scales. However, more robust black hole mass estimates would improve the accuracy of the Eddington ratio estimates for these objects. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of whole-body magnetic resonance imaging (MRI) including diffusion-weighted imaging with background signal suppression (DWIBS) for preoperative assessment of non-small-cell lung cancer (NSCLC) in comparison to (18)F-fluorodeoxyglucose (18)FDG) positron emission tomography/computed tomography (PET/CT).Methods: Thirty-three patients with suspected NSCLC were enrolled. Patients were examined before surgery with PET/CT and whole-body MRI including T1-weighted turbo spin echo (TSE), T2-weighted short tau inversion recovery (STIR) and DWIBS sequences (b = 0/800). Histological or cytological specimens were taken as standard of reference.Results: Whole-body MRI with DWIBS as well as PET/CT provided diagnostic image quality in all cases. Sensitivity for primary tumour detection: MRI 93%, PET/CT 98%. T-staging accuracy: MRI 63%, PET/CT 56%. N-staging accuracy: MRI 66%, PET/CT 71%. UICC staging accuracy: MRI 66%, PET/CT 74%. Sensitivity for metastatic involvement of individual lymph node groups: MRI 44%, PET/CT 47%. Specificity for individual non-metastatic lymph node groups: MRI 93%, PET/CT 96%. Assessment accuracy for individual lymph node groups: MRI 85%, PET/CT 88%. Observer agreement rate for UICC staging: MRI 74%, PET/CT 90%.Conclusion: Whole-body MRI with DWIBS provides comparable results to PET/CT in staging of NSCLC, but shows no superiority. Most relevant challenges for both techniques are T-staging accuracy and sensitivity for metastatic lymph node involvement.Key Points: Numerous radiological methods are available for the crucial staging of lung cancer. Whole-body DWIBS MRI provides comparable results to PET/CT in NSCLC staging. No evident superiority of whole-body DWIBS over PET/CT in NSCLC staging. Challenges for both techniques are T-staging and detection of small metastases. [ABSTRACT FROM AUTHOR]

Objectives: To implement, examine, and compare three multichannel transmit/receive coil configurations for cardiovascular MR (CMR) at 7T.Methods: Three radiofrequency transmit-receive (TX/RX) coils with 4-, 8-, and 16-coil elements were used. Ten healthy volunteers (seven males, age 28 ± 4 years) underwent CMR at 7T. For all three RX/TX coils, 2D CINE FLASH images of the heart were acquired. Cardiac chamber quantification, signal-to-noise ratio (SNR) analysis, parallel imaging performance assessment, and image quality scoring were performed.Results: Mean total examination time was 29 ± 5 min. All images obtained with the 8- and 16-channel coils were diagnostic. No significant difference in ejection fraction (EF) (P > 0.09) or left ventricular mass (LVM) (P > 0.31) was observed between the coils. The 8- and 16-channel arrays yielded a higher mean SNR in the septum versus the 4-channel coil. The lowest geometry factors were found for the 16-channel coil (mean ± SD 2.3 ± 0.5 for R = 4). Image quality was rated significantly higher (P < 0.04) for the 16-channel coil versus the 8- and 4-channel coils.Conclusions: All three coil configurations are suitable for CMR at 7.0T under routine circumstances. A larger number of coil elements enhances image quality and parallel imaging performance but does not impact the accuracy of cardiac chamber quantification.Key Points: • Cardiac chamber quantification using 7.0T magnetic resonance imaging is feasible. • Examination times for cardiac chamber quantification at 7.0T match current clinical practice. • Multichannel transceiver RF technology facilitates improved image quality and parallel imaging performance. • Increasing the number of RF channels does not influence cardiac chamber quantification. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes. Methods: In total, 605 patients aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure. Results: Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction. Conclusions/interpretation: This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to 'unmasking' these patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Galactic nuclei should contain a cluster of stars and compact objects in the vicinity of the central supermassive black hole due to stellar evolution, minor mergers and gravitational dynamical friction. By analogy with protoplanetary migration, nuclear cluster objects (NCOs) can migrate in the accretion discs that power active galactic nuclei (AGN) by exchanging angular momentum with disc gas. Here we show that an individual NCO undergoing runaway outward migration comparable to type III protoplanetary migration can generate an accretion rate corresponding to Seyfert AGN or quasar luminosities. Multiple migrating NCOs in an AGN disc can dominate traditional viscous disc accretion, and at large disc radii, ensemble NCO migration and accretion could provide sufficient heating to prevent the gravitational instability from consuming disc gas in star formation. The magnitude and energy of the X-ray soft excess observed at ∼0.1-1 keV in Seyfert AGN could be explained by a small population of ∼102-103 accreting stellar mass black holes or a few ULXs. NCO migration and accretion in AGN discs are therefore extremely important mechanisms to add to realistic models of AGN discs. [ABSTRACT FROM AUTHOR]

We present XMM-Newton observations of three active galactic nuclei (AGNs) taken as part of a hunt to find very heavily obscured Compton-thick AGNs. For obscuring columns greater than 1025 cm-2, AGNs are only visible at energies below 10 keV via reflected/scattered radiation, characterized by a flat power law. We therefore selected three objects (ESO 417-G006, IRAS 05218-1212, and MCG - 01-05-047) from the Swift Burst Alert Telescope (BAT) hard X-ray survey catalog with Swift X-ray Telescope (XRT) 0.5-10 keV spectra with flat power-law indices as candidate Compton-thick sources for follow-up observations with the more sensitive instruments on XMM-Newton. The XMM spectra, however, rule out reflection-dominated models based on the weakness of the observed Fe Kα lines. Instead, the spectra are well fit by a model of a power-law continuum obscured by a Compton-thin absorber plus a soft excess. This result is consistent with previous follow-up observations of two other flat-spectrum BAT-detected AGNs. Thus, out of the six AGNs in the 22 month BAT catalog with apparently flat Swift XRT spectra, all five that have had follow-up observations are not likely Compton thick. We also present new optical spectra of two of these objects, IRAS 05218-1212 and MCG -01-05-047. Interestingly, though both the AGNs have similar X-ray spectra, their optical spectra are completely different, adding evidence against the simplest form of the geometric unified model of AGNs. IRAS 05218-1212 appears in the optical as a Seyfert 1, despite the ~8.5 x 1022 cm-2 line-of-sight absorbing column indicated by its X-ray spectrum. MCG - 01-05-047's optical spectrum shows no sign of AGN activity; it appears as a normal galaxy. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

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Small- and intermediate-mass black holes should be expected in galactic nuclei as a result of stellar evolution, minor mergers and gravitational dynamical friction. If these minor black holes accrete as X-ray binaries or ultraluminous X-ray sources (ULXs) and are associated with star formation, they could account for observations of many low-luminosity active galactic nuclei (AGN) or low-ionization nuclear emission regions (LINERs). Accreting and inspiralling intermediate-mass black holes could provide a crucial electromagnetic counterpart to strong gravitational wave signatures, allowing tests of strong gravity. Here we discuss observational signatures of minor black holes in galactic nuclei, and we demonstrate that optical line ratios observed in LINERs or transition-type objects can be produced by an ionizing radiation field from ULXs. We conclude by discussing constraints from existing observations as well as candidates for future study. [ABSTRACT FROM AUTHOR]

Objective: This study analyses the diagnostic potential of Diffusion-Weighted Imaging with Background Suppression (DWIBS) in the detection of focal bone marrow lesions from multiple myeloma. The signal and contrast properties of DWIBS are evaluated in correlation with the serum concentration of M-component (MC) and compared with established T1- and T2-weighted sequences.Methods: Data from 103 consecutive studies in 81 patients are analysed retrospectively. Signal intensities and apparent Diffusion Coefficients (ADC) of 79 focal lesions in the lumbar spine or pelvis of 38 patients are determined and contrast-to-noise-ratio (CNR) is calculated. Data from patients with low (<20 g/L) and high (>20 g/dL) MC are evaluated separately.Results: Signal intensities of focal myeloma lesions on T2w-STIR vary significantly depending on the MC, which leads to a loss in CNR in patients with high MC. No signal variation is observed for T1w-TSE and DWIBS. The CNR values provided by DWIBS in patients with high MC are slightly higher than those of T2w-STIR. ADC values in patients with low MC are significantly higher than in patients with high MC.Conclusion: Whole-body DWIBS has the potential to improve the conspicuity of focal myeloma lesions and provides additional biological information by ADC quantification. [ABSTRACT FROM AUTHOR]

Type 3 Von Willebrand disease (VWD) is a rare, severe, autosomal recessive bleeding disorder. In our institution, we follow 17 children with type 3 VWD. We have observed a high prevalence of dental disease in these patients prompting us to undertake a retrospective review of our cohort of patients with type 3 VWD to catalogue the extent of their dental disease. Sixteen of these patients have been assessed by our dentistry department. Five children have undergone minor dental procedures (e.g. restorations, stainless steel crowns) and seven major procedures (e.g. dental extractions, pulpotomies and root canal treatments). These patients have collectively used 85 400 (ristocetin cofactor) IU of Humate-P on dental procedures alone. In addition to the considerable costs of factor are the cost of operating room time, dentists' costs, and the cost of other topical haemostatic agents (e.g. Tisseel) used during their dental procedures. As such there is considerable morbidity and cost from dental disease in these patients that is much higher than what is seen in patients with haemophilia or in the normal paediatric population. We speculate that the combination of these patients having a significant mucosal bleeding disorder together with various socioeconomic factors contribute to the significant degree of dental disease seen in this group of patients. We would suggest that better preventive dental care needs to be provided to these patients to avoid the considerable morbidity and very high burden of dental disease in type 3 VWD. [ABSTRACT FROM AUTHOR]

Context: Optimal treatment to postpone functional decline in patients with dementia is not established.Objective: To test a nonpharmacologic intervention realigning environmental demands with patient capabilities.Design, Setting, and Participants: Prospective 2-group randomized trial (Care of Persons with Dementia in their Environments [COPE]) involving patients with dementia and family caregivers (community-living dyads) recruited from March 2006 through June 2008 in Pennsylvania.Interventions: Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits; obtained blood and urine samples; and trained families in home safety, simplifying tasks, and stress reduction. Control group caregivers received 3 telephone calls and educational materials.Main Outcome Measures: Functional dependence, quality of life, frequency of agitated behaviors, and engagement for patients and well-being, confidence using activities, and perceived benefits for caregivers at 4 months.Results: Of 284 dyads screened, 270 (95%) were eligible and 237 (88%) randomized. Data were collected from 209 dyads (88%) at 4 months and 173 (73%) at 9 months. At 4 months, compared with controls, COPE patients had less functional dependence (adjusted mean difference, 0.24; 95% CI, 0.03-0.44; P = .02; Cohen d = 0.21) and less dependence in instrumental activities of daily living (adjusted mean difference, 0.32; 95% CI, 0.09-0.55; P = .007; Cohen d = 0.43), measured by a 15-item scale modeled after the Functional Independence Measure; COPE patients also had improved engagement (adjusted mean difference, 0.12; 95% CI, 0.07-0.22; P = .03; Cohen d = 0.26), measured by a 5-item scale. COPE caregivers improved in their well-being (adjusted mean difference in Perceived Change Index, 0.22; 95% CI, 0.08-0.36; P = .002; Cohen d = 0.30) and confidence using activities (adjusted mean difference, 0.81; 95% CI, 0.30-1.32; P = .002; Cohen d = 0.54), measured by a 5-item scale. By 4 months, 64 COPE dyads (62.7%) vs 48 control group dyads (44.9%) eliminated 1 or more caregiver-identified problems (chi(2/1) = 6.72, P = . 01).Conclusion: Among community-living dyads, a nonpharmacologic biobehavioral environmental intervention compared with control resulted in better outcomes for COPE dyads at 4 months. Although no group differences were observed at 9 months for patients, COPE caregivers perceived greater benefits.Trial Registration: clinicaltrials.gov Identifier: NCT00259454. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) 16, 151–155 Objective: To develop a novel test for chronic ulcerative stomatitis (CUS), a chronic immunologically mediated condition that produces oral ulcerations. Current diagnostic methods require expensive and technically demanding in situ immunofluorescence (IF) studies. Design: An Enzyme-Linked ImmunoSorbent Assay (ELISA) was prepared and tested with serum samples from patients with CUS and negative controls. Materials and Methods: The N-terminal portion of the CUS autoantigen, ΔNp63α, was produced as a purified recombinant protein and used to coat ELISA plates. Sera from 25 patients with CUS and 16 negative controls were analyzed for reactive antibodies. The optimal cut-offs for positive and negative samples were determined. Main outcome measures: The optimal cut-off of 0.236 resulted in a sensitivity and specificity of the ELISA of 0.80 and 0.75, respectively (exact 95% confidence intervals, P-value of <0.001). Results: The ELISA developed in this study provides a novel and reliable diagnostic assessment to distinguish CUS from other oral ulcerative diseases. Conclusions: Immunoassay will allow the true incidence and prevalence of CUS to be determined in future studies. When combined with clinical correlations, the ELISA results will facilitate the evaluation of the prognostic utility of antibody titers and allow correlation with treatment responses in individual CUS cases. [ABSTRACT FROM AUTHOR]

The Swift/Burst Alert Telescope (BAT) 9-month catalogue of active galactic nuclei (AGN) provides an unbiased census of local supermassive black hole accretion, and probes to all but the highest levels of absorption in AGN. We explore a method for characterizing the bolometric output of both obscured and unobscured AGN by combining the hard X-ray data from the Swift/BAT instrument (14–195keV) with the reprocessed infrared (IR) emission as seen with the Infrared Astronomical Satellite ( IRAS) all-sky surveys. This approach bypasses the complex modifications to the spectral energy distribution introduced by absorption in the optical, UV and 0.1–10 keV regimes and provides a long-term, average picture of the bolometric output of these sources. We broadly follow the approach of Pozzi et al. for calculating the bolometric luminosities by adding nuclear IR and hard X-ray luminosities, and consider different approaches for removing non-nuclear contamination in the large-aperture IRAS fluxes. Using mass estimates from the black hole mass-host galaxy bulge luminosity relation, we present the Eddington ratios and 2–10 keV bolometric corrections for a subsample of 63 AGN (35 obscured and 28 unobscured) from the Swift/BAT catalogue, and confirm previous indications of a low Eddington ratio distribution for both samples. Importantly, we find a tendency for low bolometric corrections (typically 10–30) for the obscured AGN in the sample (with a possible rise from ∼15 for to ∼32 above this), providing a hitherto unseen window on to accretion processes in this class of AGN. This finding is of key importance in calculating the expected local black hole mass density from the X-ray background since it is composed of emission from a significant population of such obscured AGN. Analogous studies with high-resolution IR data and a range of alternative models for the torus emission will form useful future extensions to this work. [ABSTRACT FROM AUTHOR]

We present simultaneous optical-to-X-ray spectral energy distributions (SEDs) from Swift's X-ray and UV–optical telescopes (XRTs and UVOTs) for a well-selected sample of 26 low-redshift active galactic nuclei (AGN) from the Swift/Burst Alert Telescope 9-month catalogue, the largest well-studied, hard X-ray-selected survey of local AGN to date. Our sub-sample consists of AGN with low intrinsic X-ray absorption and minimal spectral complexity, to more accurately recover the intrinsic accretion luminosity in these sources. We perform a correction for host galaxy contamination in all available UVOT filter images to recover the intrinsic AGN emission and estimate intrinsic dust extinction from the resultant nuclear SEDs. Black hole mass estimates are determined from the host galaxy Two-Micron All-Sky Survey K-band bulge luminosity. Accretion rates determined from our SEDs are on average low (Eddington ratios ) and hard X-ray bolometric corrections cluster at ∼10–20, in contrast with the higher values seen for quasars. An average SED for the 22 low accretion rate objects is presented, with and without correction for extinction. Significant dust reddening is found in some objects despite the selection of low NH objects, emphasizing the complex relationship between these two types of absorption. We do not find a correlation of the optical-to-X-ray spectral index with the Eddington ratio, regardless of the optical reference wavelength chosen for defining the spectral index. An anticorrelation of bolometric correction with black hole mass may reinforce ‘cosmic downsizing’ scenarios, since the higher bolometric corrections at low mass would boost accretion rates in local, lower mass black holes. We also perform a basic analysis of the UVOT-derived host galaxy colours for our sample and find hosts cluster near the ‘green valley’ of the colour–magnitude diagram, but better quality images are needed for a more definitive analysis. The low accretion rates and bolometric corrections found for this representative low-redshift sample are of particular importance for studies of AGN accretion history. [ABSTRACT FROM AUTHOR]

Outward radiation pressure can exceed the inward gravitational pull on gas clouds in the neighbourhood of a luminous active galactic nucleus (AGN). This creates a forbidden region for long-lived dusty clouds in the observed columnn density–Eddington fraction plane. (The Eddington fraction is the ratio of the bolometric luminosity of an AGN to the Eddington limit for its black hole mass.) The Swift/Burst Alert Telescope catalogue is the most complete hard X-ray selected sample of AGN and has 97 low-redshift AGN with measured column densities and inferred black hole masses. Eddington fractions for the sources have been obtained using recent bolometric corrections and the sources have been plotted on the plane. Only one source lies in the forbidden region and it has a large value of due to an ionized warm absorber, for which radiation pressure is reduced. The effective Eddington limit for the source population indicates that the high column density clouds in the more luminous objects lie within the inner few pc, where the central black hole provides at least half the mass. Our result shows that radiation pressure does affect the presence of gas clouds in the inner galaxy bulge. We discuss briefly how the plane may evolve to higher redshift, when feedback due to radiation pressure may have been strong. [ABSTRACT FROM AUTHOR]

Background There is a paucity of research on the relationship between parental knowledge, parenting and parenting self-efficacy, and some inconsistencies have been reported in the literature. Method Parent knowledge of effective parenting strategies was assessed among 68 parents from a non-clinic sample, who also completed questionnaires relating to parenting confidence, quality of parenting and child behaviour. Results Parents with greater knowledge tended to be less dysfunctional, and reported significantly higher education and income levels. Parenting confidence explained a significant proportion of the variance in reported frequency of disruptive child behaviour while knowledge did not independently contribute to the prediction. However, the relationship between parenting confidence and dysfunctional parenting was moderated by the level of knowledge. There was a stronger negative relationship between confidence and dysfunctional parenting when knowledge level was low than when it was high. Post hoc analyses indicated that the relationship between parenting knowledge and disruptive child behaviour was moderated by the level of parenting dysfunction. Parenting knowledge and reported frequency of disruptive behaviour were positively related when the level of dysfunction was low, but were unrelated when it was high. Conclusions Parents with low levels of knowledge and confidence in their parenting may be at greater risk of dysfunctional parenting and might benefit from interventions designed to enhance both knowledge and confidence. Results are interpreted in relation to inconsistencies with previous research and implications for future methodologies. [ABSTRACT FROM AUTHOR]