The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis ...(hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome.
We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up.
Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval CI, 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups.
Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).
The monitoring of adverse drug reactions (ADRs) through pharmacovigilance is vital to patient safety. Spontaneous reporting of ADRs is one method of pharmacovigilance, and in the UK this is ...undertaken through the Yellow Card Scheme (YCS). Yellow Card reports are submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) by post, telephone or via the internet. The MHRA electronically records and reviews information submitted so that important safety issues can be detected. While previous studies have shown differences between patient and health-care professional (HCP) reports for the types of drugs and reactions reported, relatively little is known about the pharmacovigilance impact of patient reports. There have also been few studies on the views and experiences of patients/consumers on the reporting of suspected ADRs.
To evaluate the pharmacovigilance impact of patient reporting of ADRs by analysing reports of suspected ADRs from the UK YCS and comparing reports from patients and HCPs. To elicit the views and experiences of patients and the public about patient reporting of ADRs.
(1) Literature review and survey of international experiences of consumer reporting of ADRs; (2) descriptive analysis of Yellow Card reports; (3) signal generation analysis of Yellow Card reports; (4) qualitative analysis of Yellow Card reports; (5) questionnaire survey of patients reporting on Yellow Cards; (6) qualitative analysis of telephone interviews with patient reporters to the scheme; (7) qualitative analysis of focus groups and usability testing of the patient YCS; and (8) national omnibus telephone survey of public awareness of the YCS.
Patients (n = 5180) and HCPs (n = 20,949) submitting Yellow Card reports from October 2005 to September 2007. Respondents to questionnaire survey (n = 1362). Participants at focus groups and usability testing sessions (n = 40). National omnibus telephone survey (n = 2028).
The literature review included studies in English from across the world. All other components included populations from the UK; the omnibus survey was restricted to Great Britain.
None.
Characteristics of patient reports: types of drug and suspected ADR reported; seriousness of reports; and content of reports. The relative contributions of patient reports and of HCP reports to signal generation. Views and experiences of patient reporters. Views of members of the public about the YCS, including user-friendliness and usability of different ways of patient reporting. Public awareness of the YCS. Suggestions for improving patient reporting to the YCS.
Compared with HCPs, patient reports to the YCS contained a higher median number of suspected ADRs per report, and described reactions in more detail. The proportions of reports categorised as 'serious' were similar; the patterns of drugs and reactions reported differed. Patient reports were richer in their descriptions of reactions than those from HCPs, and more often noted the effects of ADRs on patients' lives. Combining patient and HCP reports generated more potential signals than HCP reports alone; some potential signals in the 'HCP-only' data set were lost when combined with patient reports, but fewer than those gained; the addition of patient reports to HCP reports identified 47 new 'serious' reactions not previously included in 'Summaries of Product Characteristics'. Most patient reporters found it fairly easy to make reports, although improvements to the scheme were suggested, including greater publicity and the redesign of web- and paper-based reporting systems. Among members of the public, 8.5% were aware of the YCS in 2009.
Patient reporting of suspected ADRs has the potential to add value to pharmacovigilance by reporting types of drugs and reactions different from those reported by HCPs; generating new potential signals; and describing suspected ADRs in enough detail to provide useful information on likely causality and impact on patients' lives. These findings suggest that further promotion of patient reporting to the YCS is justified, along with improvements to existing reporting systems. In order of priority, future work should include further investigation of (1) the pharmacovigilance impact of patient reporting in a longer-term study; (2) the optimum approach to signal generation analysis of patient and HCP reports; (3) the burden of ADRs in terms of impact on patients' lives; (4) the knowledge and attitudes of HCPs towards patient reporting of ADRs; (5) the value of using patient reports of ADRs to help other patients and HCPs who are seeking information on patient experiences of ADRs; and (6) the impact of increasing publicity and/or enhancements to reporting systems on the numbers and types of Yellow Card reports from patients.
The National Institute for Health Research Health Technology Assessment programme.
Laser wakefield accelerators promise to revolutionize many areas of accelerator science. However, one of the greatest challenges to their widespread adoption is the difficulty in control and ...optimization of the accelerator outputs due to coupling between input parameters and the dynamic evolution of the accelerating structure. Here, we use machine learning techniques to automate a 100 MeV-scale accelerator, which optimized its outputs by simultaneously varying up to six parameters including the spectral and spatial phase of the laser and the plasma density and length. Most notably, the model built by the algorithm enabled optimization of the laser evolution that might otherwise have been missed in single-variable scans. Subtle tuning of the laser pulse shape caused an 80% increase in electron beam charge, despite the pulse length changing by just 1%.
Experts have proposed removing obsessive-compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity ...and familiality data to inform these issues.
Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).
Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive-compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.
On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
We present an analysis of , O iii88, N ii122, and far-infrared (FIR) fine-structure line observations obtained with Herschel/PACS, for ∼240 local luminous infrared galaxies (LIRGs) in the Great ...Observatories All-sky LIRG Survey. We find pronounced declines ("deficits") of line-to-FIR continuum emission for N ii122, , and as a function of FIR color and infrared luminosity surface density, . The median electron density of the ionized gas in LIRGs, based on the N ii122/N ii205 ratio, is = 41 cm−3. We find that the dispersion in the deficit of LIRGs is attributed to a varying fractional contribution of photodissociation regions (PDRs) to the observed emission, f( ) = / , which increases from ∼60% to ∼95% in the warmest LIRGs. The / ratio is tightly correlated with the PDR gas kinetic temperature in sources where is not optically thick or self-absorbed. For each galaxy, we derive the average PDR hydrogen density, , and intensity of the interstellar radiation field, G, in units of and find G/ ratios of ∼0.1-50 cm3, with ULIRGs populating the upper end of the distribution. There is a relation between G/ and , showing a critical break at 5 × 1010 L kpc−2. Below , G/ remains constant, 0.32 cm3, and variations in are driven by the number density of star-forming regions within a galaxy, with no change in their PDR properties. Above , G/ increases rapidly with , signaling a departure from the typical PDR conditions found in normal star-forming galaxies toward more intense/harder radiation fields and compact geometries typical of starbursting sources.
The range of possibilities for future climate evolution needs to be taken into account when planning climate change mitigation and adaptation strategies. This requires ensembles of multi-decadal ...simulations to assess both chaotic climate variability and model response uncertainty. Statistical estimates of model response uncertainty, based on observations of recent climate change, admit climate sensitivities-defined as the equilibrium response of global mean temperature to doubling levels of atmospheric carbon dioxide-substantially greater than 5 K. But such strong responses are not used in ranges for future climate change because they have not been seen in general circulation models. Here we present results from the 'climateprediction.net' experiment, the first multi-thousand-member grand ensemble of simulations using a general circulation model and thereby explicitly resolving regional details. We find model versions as realistic as other state-of-the-art climate models but with climate sensitivities ranging from less than 2 K to more than 11 K. Models with such extreme sensitivities are critical for the study of the full range of possible responses of the climate system to rising greenhouse gas levels, and for assessing the risks associated with specific targets for stabilizing these levels.
Extracellular vesicles (EVs) form an endogenous transport system for intercellular transfer of biological cargo, including RNA, that plays a pivotal role in physiological and pathological processes. ...Unfortunately, whereas biological effects of EV-mediated RNA transfer are abundantly studied, regulatory pathways and mechanisms remain poorly defined due to a lack of suitable readout systems. Here, we describe a highly-sensitive CRISPR-Cas9-based reporter system that allows direct functional study of EV-mediated transfer of small non-coding RNA molecules at single-cell resolution. Using this CRISPR operated stoplight system for functional intercellular RNA exchange (CROSS-FIRE) we uncover various genes involved in EV subtype biogenesis that play a regulatory role in RNA transfer. Moreover we identify multiple genes involved in endocytosis and intracellular membrane trafficking that strongly regulate EV-mediated functional RNA delivery. Altogether, this approach allows the elucidation of regulatory mechanisms in EV-mediated RNA transfer at the level of EV biogenesis, endocytosis, intracellular trafficking, and RNA delivery.
Krebs cycle intermediates traditionally link to oxidative phosphorylation whilst also making key cell components. It is now clear that some of these metabolites also act as signals. Succinate plays ...an important role in inflammatory, hypoxic, and metabolic signaling, while itaconate (from another Krebs cycle intermediate, cis-aconitate) has an anti-inflammatory role.
The metabolites succinate and itaconate have emerged as key signaling molecules linking mitochondrial function to the rest of the cell across several areas of cell function.
GOALS: The Great Observatories All-Sky LIRG Survey Armus, L.; Mazzarella, J. M.; Evans, A. S. ...
Publications of the Astronomical Society of the Pacific,
06/2009, Letnik:
121, Številka:
880
Journal Article
Recenzirano
Odprti dostop
The Great Observatories All-Sky LIRG Survey (GOALS20) combines data from NASA’sSpitzer Space Telescope,
Chandra X-Ray Observatory,
Hubble Space Telescope(HST), andGalaxy Evolution Explorer(GALEX) ...observatories, together with ground-based data, into a comprehensive imaging and spectroscopic survey of over 200 low-redshift (
z < 0.088
z
<
0.088
), Luminous Infrared Galaxies (LIRGs). The LIRGs are a complete subset of theIRASRevised Bright Galaxy Sample (RBGS), which comprises 629 extragalactic objects with 60 μm flux densities above 5.24 Jy, and Galactic latitudes above five degrees. The LIRGs targeted in GOALS span the full range of nuclear spectral types defined via traditional optical line-ratio diagrams (type-1 and type-2 AGN, LINERs, and starbursts) as well as interaction stages (major mergers, minor mergers, and isolated galaxies). They provide an unbiased picture of the processes responsible for enhanced infrared emission in galaxies in the local Universe. As an example of the analytic power of the multiwavelength GOALS data set, we presentSpitzer, Chandra, HST,andGALEXimages and spectra for the interacting system VV 340 (IRAS
F14547 + 2449
F
14547
+
2449
). TheSpitzerMIPS imaging data indicates that between 80–95% of the total far-infrared emission (or about5 × 1011 L
⊙
5
×
10
11
L
⊙
) originates in VV 340 north. While theSpitzerIRAC colors of VV 340 north and south are consistent with star-forming galaxies, both theSpitzerIRS andChandraACIS data indicate the presence of an AGN in VV 340 north. The observed line fluxes, without correction for extinction, imply that the AGN accounts for less than 10%–20% of the observed infrared emission. The X-ray data are consistent with a heavily absorbed (
N
H
≥1024 cm-2
N
H
≥
10
24
cm
-
2
) AGN. The GALEX far and near-UV fluxes imply a extremely large infrared “excess” (IRX) for the system (FIR/Ffuv ∼ 81
F
IR
/
F
fuv
∼
81
) which is well above the correlation seen in starburst galaxies. Most of this excess is driven by VV 340 N, which has an IR excess of nearly 400. The VV 340 system seems to be comprised of two very different galaxies: an infrared luminous edge-on galaxy (VV 340 north) that dominates the long-wavelength emission from the system, which hosts a buried AGN; and a face-on starburst (VV 340 south) that dominates the short-wavelength emission.
High-power lasers that fit into a university-scale laboratory can now reach focused intensities of more than 1019 W cm-2 at high repetition rates. Such lasers are capable of producing beams of ...energetic electrons, protons and γ-rays. Relativistic electrons are generated through the breaking of large-amplitude relativistic plasma waves created in the wake of the laser pulse as it propagates through a plasma, or through a direct interaction between the laser field and the electrons in the plasma. However, the electron beams produced from previous laser-plasma experiments have a large energy spread, limiting their use for potential applications. Here we report high-resolution energy measurements of the electron beams produced from intense laser-plasma interactions, showing that-under particular plasma conditions-it is possible to generate beams of relativistic electrons with low divergence and a small energy spread (less than three per cent). The monoenergetic features were observed in the electron energy spectrum for plasma densities just above a threshold required for breaking of the plasma wave. These features were observed consistently in the electron spectrum, although the energy of the beam was observed to vary from shot to shot. If the issue of energy reproducibility can be addressed, it should be possible to generate ultrashort monoenergetic electron bunches of tunable energy, holding great promise for the future development of 'table-top' particle accelerators.
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