4,646 research outputs found
QT prolongation in the STREAM Stage 1 Trial
BACKGROUND: STREAM (Standardized Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB) Stage 1 demonstrated non-inferior efficacy of a shortened regimen (the Short regimen) for rifampicin-resistant TB (RR-TB) compared to the contemporaneous WHO-recommended regimen. This regimen included moxifloxacin and clofazimine, known to cause QT prolongation, and severe prolongation was more common on the Short regimen. Here we investigate risk factors for QT prolongation with the Short regimen.METHODS: Data from patients prescribed the Short regimen (n = 282) were analysed to identify risk factors for severe QT prolongation (QT/QTcF â„500 ms or â„60 ms increase in QTcF from baseline).RESULTS: Of the 282 patients on the Short regimen, 94 (33.3%) developed severe QT prolongation: 31 QT/QTcF â„500 ms; 92 experienced â„60 ms QTcF increase from baseline. The median time to QT/QTcF â„500 ms was 20 weeks (IQR 8-28), and the time to â„60 ms increase from baseline was 18 weeks (IQR 8-28). Prolongation â„500 ms was most frequent in patients from Mongolia (10/22, 45.5%) compared with 3.5-11.9% at other sites, P < 0.001. Higher baseline QTcF increased risk of prolongation to â„500 ms (QTcF â„400 ms: OR 5.99, 95% CI 2.04-17.62).CONCLUSION: One third of patients on the Short regimen developed severe QT prolongation. QT/QTcF â„500 ms was more common in patients from Mongolia and in those with a higher baseline QTcF, which may have implications for implementation of treatment
A massive reservoir of low-excitation molecular gas at high redshift
Molecular hydrogen is an important component of galaxies because it fuels
star formation and accretion onto AGN, the two processes that generate the
large infrared luminosities of gas-rich galaxies. Observations of spectral-line
emission from the tracer molecule CO are used to probe the properties of this
gas. But the lines that have been studied in the local Universe, mostly the
lower rotational transitions of J = 1-0 and J = 2-1, have hitherto been
unobservable in high-redshift galaxies. Instead, higher transitions have been
used, although the densities and temperatures required to excite these higher
transitions may not be reached by much of the gas. As a result, past
observations may have underestimated the total amount of molecular gas by a
substantial amount. Here we report the discovery of large amounts of
low-excitation molecular gas around the infrared-luminous quasar, APM
08279+5255 at z = 3.91, using the two lowest excitation lines of 12CO (J = 1-0
and J = 2-1). The maps confirm the presence of hot and dense gas near the
nucleus, and reveal an extended reservoir of molecular gas with low excitation
that is 10 to 100 times more massive than the gas traced by higher-excitation
observations. This raises the possibility that significant amounts of
low-excitation molecular gas may lurk in the environments of high-redshift (z >
3) galaxies.Comment: To appear as a Letter to Nature, 4th January 200
The Quantized Hall Insulator: A New Insulator in Two-Dimensions
Quite generally, an insulator is theoretically defined by a vanishing
conductivity tensor at the absolute zero of temperature. In classical
insulators, such as band insulators, vanishing conductivities lead to diverging
resistivities. In other insulators, in particular when a high magnetic field
(B) is added, it is possible that while the magneto-resistance diverges, the
Hall resistance remains finite, which is known as a Hall insulator. In this
letter we demonstrate experimentally the existence of another, more exotic,
insulator. This insulator, which terminates the quantum Hall effect series in a
two-dimensional electron system, is characterized by a Hall resistance which is
approximately quantized in the quantum unit of resistance h/e^2. This insulator
is termed a quantized Hall insulator. In addition we show that for the same
sample, the insulating state preceding the QHE series, at low-B, is of the HI
kind.Comment: 4 page
It's the product not the polymer: Rethinking plastic pollution
Mismanaged plastic waste poses a complex threat to the environments that it contaminates, generating considerable concern from academia, industry, politicians, and the general public. This concern has driven global action that presents a unique opportunity for widespread environmental engagement beyond the immediate problem of the persistence of plastic in the environment. But for such an opportunity to be realized, it is vital that the realities of plastic waste are not misrepresented or exaggerated. Hotspots of plastic pollution, which are often international in their source, present complex environmental problems in certain parts of the world. Here we argue, however, that the current discourse on plastic waste overshadows greater threats to the environment and society at a global scale. Antiplastic sentiments have been exploited by politicians and industry, where reducing consumers' plastic footprints are often confused by the seldomâchallenged veil of environmental consumerism, or âgreenwashing.â Plastic is integral to much of modern day life, and regularly represents the greener facilitator of society's consumption. We conclude that it is the product, not the polymer that is driving the issue of plastic waste. Contemporary consumption and disposal practices are the root of much of the anthropogenic waste in the environment, plastic, or not. Effective environmental action to minimize plastic in the environment should be motivated by changes in consumption practices, policies, and product design, and should be informed by objective science and legislation
Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval
Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed
The extraordinary evolutionary history of the reticuloendotheliosis viruses
The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVsâunequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events
Resection of the liver for colorectal carcinoma metastases - A multi-institutional study of long-term survivors
In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. © 1988 American Society of Colon and Rectal Surgeons
Improving appropriate polypharmacy for older people in primary care: selecting components of an evidence-based intervention to target prescribing and dispensing
Background
The use of multiple medicines (polypharmacy) is increasingly common in older people. Ensuring that patients receive the most appropriate combinations of medications (appropriate polypharmacy) is a significant challenge. The quality of evidence to support the effectiveness of interventions to improve appropriate polypharmacy is low. Systematic identification of mediators of behaviour change, using the Theoretical Domains Framework (TDF), provides a theoretically robust evidence base to inform intervention design. This study aimed to (1) identify key theoretical domains that were perceived to influence the prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists, and (2) map domains to associated behaviour change techniques (BCTs) to include as components of an intervention to improve appropriate polypharmacy in older people in primary care.
Methods
Semi-structured interviews were conducted with members of each healthcare professional (HCP) group using tailored topic guides based on TDF version 1 (12 domains). Questions covering each domain explored HCPsâ perceptions of barriers and facilitators to ensuring the prescribing and dispensing of appropriate polypharmacy to older people. Interviews were audio-recorded and transcribed verbatim. Data analysis involved the framework method and content analysis. Key domains were identified and mapped to BCTs based on established methods and discussion within the research team.
Results
Thirty HCPs were interviewed (15 GPs, 15 pharmacists). Eight key domains were identified, perceived to influence prescribing and dispensing of appropriate polypharmacy: âSkillsâ, âBeliefs about capabilitiesâ, âBeliefs about consequencesâ, âEnvironmental context and resourcesâ, âMemory, attention and decision processesâ, âSocial/professional role and identityâ, âSocial influencesâ and âBehavioural regulationâ. Following mapping, four BCTs were selected for inclusion in an intervention for GPs or pharmacists: âAction planningâ, âPrompts/cuesâ, âModelling or demonstrating of behaviourâ and âSalience of consequencesâ. An additional BCT (âSocial support or encouragementâ) was selected for inclusion in a community pharmacy-based intervention in order to address barriers relating to interprofessional working that were encountered by pharmacists.
Conclusions
Selected BCTs will be operationalised in a theory-based intervention to improve appropriate polypharmacy for older people, to be delivered in GP practice and community pharmacy settings. Future research will involve development and feasibility testing of this intervention
High-statistics modeling of complex pedestrian avoidance scenarios
Quantitatively modeling the trajectories and behavior of pedestrians walking
in crowds is an outstanding fundamental challenge deeply connected with the
physics of flowing active matter, from a scientific point of view, and having
societal applications entailing individual safety and comfort, from an
application perspective.
In this contribution, we review a pedestrian dynamics modeling approach,
previously proposed by the authors, aimed at reproducing some of the
statistical features of pedestrian motion. Comparing with high-statistics
pedestrian dynamics measurements collected in real-life conditions (from
hundreds of thousands to millions of trajectories), we modeled quantitatively
the statistical features of the undisturbed motion (i.e. in absence of
interactions with other pedestrians) as well as the avoidance dynamics
triggered by a pedestrian incoming in the opposite direction. This was
accomplished through (coupled) Langevin equations with potentials including
multiple preferred velocity states and preferred paths. In this chapter we
review this model, discussing some of its limitations, in view of its extension
toward a more complex case: the avoidance dynamics of a single pedestrian
walking through a crowd that is moving in the opposite direction. We analyze
some of the challenges connected to this case and present extensions to the
model capable of reproducing some features of the motion
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