In July 2012, as the four ground-based gamma-ray telescopes of the H.E.S.S. (High Energy Stereoscopic System) array reached their tenth year of operation in Khomas Highlands, Namibia, a fifth ...telescope took its first data as part of the system. This new Cherenkov detector, comprising a 614.5m2 reflector with a highly pixelized camera in its focal plane, improves the sensitivity of the current array by a factor two and extends its energy domain down to a few tens of GeV.
The present part I of the paper gives a detailed description of the fifth H.E.S.S. telescope׳s camera, presenting the details of both the hardware and the software, emphasizing the main improvements as compared to previous H.E.S.S. camera technology.
The social context of well–being Huppert, F. A.; Baylis, N.; Keverne, B. ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
09/2004, Letnik:
359, Številka:
1449
Journal Article
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Large samples of data from the World Values Survey, the US Benchmark Survey and a comparable Canadian survey are used to estimate equations designed to explore the social context of subjective ...evaluations of well-being, of happiness, and of health. Social capital, as measured by the strength of family, neighbourhood, religious and community ties, is found to support both physical health and subjective well-being. Our new evidence confirms that social capital is strongly linked to subjective well-being through many independent channels and in several different forms. Marriage and family, ties to friends and neighbours, workplace ties, civic engagement (both individually and collectively), trustworthiness and trust: all appear independently and robustly related to happiness and life satisfaction, both directly and through their impact on health.
Generalized social phobia is common, persistent, and disabling and is often treated with selective serotonin reuptake inhibitor drugs or cognitive behavioral therapy.
We compared fluoxetine (FLU), ...comprehensive cognitive behavioral group therapy (CCBT), placebo (PBO), and the combinations of CCBT/FLU and CCBT/PBO.
Randomized, double-blind, placebo-controlled trial.
Two academic outpatient psychiatric centers.
Subjects meeting a primary diagnosis of generalized social phobia were recruited via advertisement. Seven hundred twenty-two were screened, and 295 were randomized and available for inclusion in an intention-to-treat efficacy analysis; 156 (52.9%) were male, 226 (76.3%) were white, and mean age was 37.1 years.
Treatment lasted for 14 weeks. Fluoxetine and PBO were administered at doses from 10 mg/d to 60 mg/d (or equivalent). Group comprehensive cognitive behavioral therapy was administered weekly for 14 sessions.
An independent blinded evaluator assessed response with the Brief Social Phobia Scale and Clinical Global Impressions scales as primary outcomes. A videotaped behavioral assessment served as a secondary outcome, using the Subjective Units of Distress Scale. Adverse effects were measured by self-rating. Each treatment was compared by means of chi2 tests and piecewise linear mixed-effects models.
Clinical Global Impressions scales response rates in the intention-to-treat sample were 29 (50.9%) (FLU), 31 (51.7%) (CCBT), 32 (54.2%) (CCBT/FLU), 30 (50.8%) (CCBT/PBO), and 19 (31.7%) (PBO), with all treatments being significantly better than PBO. On the Brief Social Phobia Scale, all active treatments were superior to PBO. In the linear mixed-effects models analysis, FLU was more effective than CCBT/FLU, CCBT/PBO, and PBO at week 4; CCBT was also more effective than CCBT/FLU and CCBT/PBO. By the final visit, all active treatments were superior to PBO but did not differ from each other. Site effects were found for the Subjective Units of Distress Scale assessment, with FLU and CCBT/FLU superior to PBO at Duke University Medical Center, Durham, NC. Treatments were well tolerated.
All active treatments were superior to PBO on primary outcomes. Combined treatment did not yield any further advantage. Notwithstanding the benefits of treatment, many patients remained symptomatic after 14 weeks.
Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) ...and overall survival (OS), we carried out a meta-analysis using individual patient level trial data.
Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated.
OS data were available for 912 patients. The median PFS was 3.3months (95% CI 2.9–3.6) and 6-month PFS rate was 27% (95% CI 24–30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3cm versus <3cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2months (95% CI 9.5–11.0) and 1year OS was 43% (95% CI 40–47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS.
Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.
Impaired insight is an important contributing factor to poor treatment response and outcome in schizophrenia. Prior studies have attempted to identify the illness characteristics that underlie these ...deficits, with conflicting results regarding associations with symptoms and neurocognitive deficits. These inconsistencies may be a function of a number of methodological issues, which were addressed in this study. In a prospective, longitudinal study, 50 individuals with schizophrenia or schizoaffective disorder underwent baseline assessments upon discharge from an acute inpatient unit, and again at a 6-month follow-up. Unawareness of positive and negative symptoms were studied separately, with analyses focusing on changes in insight over time as well as associations with disorganized symptoms, depression, and card sorting deficits. Subjects showed greater insight for negative symptoms than for positive symptoms. Insight for positive symptoms improved only slightly over the follow-up period, while negative symptom awareness did not change. Insight for negative symptoms showed modest associations with card sorting deficits, while awareness for positive symptoms showed stronger associations with thought disorder, depression, and card sorting deficits. Awareness for positive symptoms in schizophrenia may be distinct from awareness of negative symptoms. Clinicians should also be aware of the multidetermined nature of impaired insight, and future research should aim to isolate distinct mechanisms that give rise to these deficits.
Background and Aims
Alagille syndrome (ALGS) is a multisystem developmental disorder characterized by bile duct (BD) paucity, caused primarily by haploinsufficiency of the Notch ligand jagged1. The ...course of the liver disease is highly variable in ALGS. However, the genetic basis for ALGS phenotypic variability is unknown. Previous studies have reported decreased expression of the transcription factor SOX9 (sex determining region Y‐box 9) in late embryonic and neonatal livers of Jag1‐deficient mice. Here, we investigated the effects of altering the Sox9 gene dosage on the severity of liver disease in an ALGS mouse model.
Approach and Results
Conditional removal of one copy of Sox9 in Jag1+/− livers impairs the biliary commitment of cholangiocytes and enhances the inflammatory reaction and liver fibrosis. Loss of both copies of Sox9 in Jag1+/− livers further worsens the phenotypes and results in partial lethality. Ink injection experiments reveal impaired biliary tree formation in the periphery of P30 Jag1+/− livers, which is improved by 5 months of age. Sox9 heterozygosity worsens the P30 biliary tree phenotype and impairs the partial recovery in 5‐month‐old animals. Notably, Sox9 overexpression improves BD paucity and liver phenotypes in Jag1+/− mice without ectopic hepatocyte‐to‐cholangiocyte transdifferentiation or long‐term liver abnormalities. Notch2 expression in the liver is increased following Sox9 overexpression, and SOX9 binds the Notch2 regulatory region in the liver. Histological analysis shows a correlation between the level and pattern of SOX9 expression in the liver and outcome of the liver disease in patients with ALGS.
Conclusions
Our results establish Sox9 as a dosage‐sensitive modifier of Jag1+/− liver phenotypes with a permissive role in biliary development. Our data further suggest that liver‐specific increase in SOX9 levels is a potential therapeutic approach for BD paucity in ALGS.
Graphene has been proposed as a particularly attractive material for the achievement of strong optical nonlinearities, in particular generation of terahertz radiation. However, owing to the ...particular symmetries of the C-lattice, second-order nonlinear effects such as difference-frequency or rectification processes are predicted to vanish in a graphene layer for optical excitations (ℏω ≫ 2E F) involving the two relativistic dispersion bands. Here we experimentally demonstrate that graphene excited by femtosecond optical pulses generate a coherent THz radiation ranging from 0.1 to 4 THz via a second-order nonlinear effect. We fully interpret its characteristics with a model describing the electron and hole states beyond the usual massless relativistic scheme. This second-order nonlinear effect is dynamical photon drag, which relies on the transfer of light momentum to the carriers by the ponderomotive electric and magnetic forces. The model highlights the key roles of next-C-neighbor couplings and of unequal electron and hole lifetimes in the observed second-order response. Finally, our results indicate that dynamical photon drag effect in graphene can provide emission up to 60 THz, opening new routes for the generation of ultrabroadband terahertz pulses.
Time‐lapse, three‐dimensional (3D) seismic surveys have imaged an accumulation of injected CO2 adjacent to the Sleipner field in the North Sea basin. The changing pattern of reflectivity suggests ...that CO2 accumulates within a series of interbedded sandstones and mudstones beneath a thick caprock of mudstone. Nine reflective horizons within the reservoir have been mapped on six surveys acquired between 1999 and 2008. These horizons have roughly elliptical planforms with eccentricities ranging between two and four. In the top half of the reservoir, horizon areas grow linearly with time. In the bottom half, horizon areas initially grow linearly for about eight years and then progressively shrink. The central portions of deeper reflective horizons dim with time. Amplitude analysis of horizons above, within, and below the reservoir show that this dimming is not solely caused by acoustic attenuation. Instead, it is partly attributable to CO2 migration and/or CO2 dissemination, which reduce the impedance contrast between sandstone and mudstone layers. Growth characteristics and permeability constraints suggest that each horizon grows by lateral spreading of a gravity current. This model is corroborated by the temporal pattern of horizon velocity pushdown beneath the reservoir. Horizon shrinkage may occur if the distal edge of a CO2‐filled layer penetrates the overlying mudstone, if the buoyant plume draws CO2 upward, or if the effective permeability of deeper mudstone layers increases once interstitial brine has been expelled. Topographic control is evident at later times and produces elliptical planforms, especially toward the top of the reservoir. Our results show that quantitative mapping and analysis of time‐lapse seismic surveys yield fluid dynamical insights which are testable, shedding light on the general problem of CO2 sequestration.
Key Points
We have mapped time‐lapse surveys and generated a set of plan form maps
The maps show how CO2 has accumulated at different levels within the reservoir
Rates of accumulation have then been used to assess different flow models
SiLC R&D: Design, present status and perspectives Lozano, M.; Orava, R.; van Remortel, N. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
09/2007, Letnik:
579, Številka:
2
Journal Article
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This paper briefly describes the main R&D objectives that are undertaken within the international R&D collaboration SiLC aiming to build the next generation of silicon tracking devices especially in ...the case of the ILC. Firstly, motivation to use silicon detectors in the tracker is explained. Then basic aspects of the design and solutions proposed are described (sensors, front-end electronics, mechanics, alignment). First results from the lab and beam test of the front-end chips and module prototypes built are shown.
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