| 1. |
- Abadie, J., et al.
(författare)
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Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts
- 2012
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 539
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Tidskriftsartikel (refereegranskat)abstract
- Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec. 17, 2009 to Jan. 8, 2010 and Sep. 2 to Oct. 20, 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with similar to 50% or better probability with a few pointings of wide-field telescopes.
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| 2. |
- Abadie, J., et al.
(författare)
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Search for gravitational waves from low mass compact binary coalescence in LIGO's sixth science run and Virgo's science runs 2 and 3
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:8
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Tidskriftsartikel (refereegranskat)abstract
- We report on a search for gravitational waves from coalescing compact binaries using LIGO and Virgo observations between July 7, 2009, and October 20, 2010. We searched for signals from binaries with total mass between 2 and 25M(circle dot); this includes binary neutron stars, binary black holes, and binaries consisting of a black hole and neutron star. The detectors were sensitive to systems up to 40 Mpc distant for binary neutron stars, and further for higher mass systems. No gravitational-wave signals were detected. We report upper limits on the rate of compact binary coalescence as a function of total mass, including the results from previous LIGO and Virgo observations. The cumulative 90% confidence rate upper limits of the binary coalescence of binary neutron star, neutron star-black hole, and binary black hole systems are 1.3 x 10(-4), 3.1 x 10(-5), and 6.4 x 10(-6) Mpc(-3) yr(-1), respectively. These upper limits are up to a factor 1.4 lower than previously derived limits. We also report on results from a blind injection challenge.
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| 3. |
- Abadie, J., et al.
(författare)
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All-sky search for periodic gravitational waves in the full S5 LIGO data
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on an all-sky search for periodic gravitational waves in the frequency band 50-800 Hz and with the frequency time derivative in the range of 0 through -6 x 10(-9) Hz/s. Such a signal could be produced by a nearby spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. After recent improvements in the search program that yielded a 10x increase in computational efficiency, we have searched in two years of data collected during LIGO's fifth science run and have obtained the most sensitive all-sky upper limits on gravitational-wave strain to date. Near 150 Hz our upper limit on worst-case linearly polarized strain amplitude h(0) is 1 x 10(-24), while at the high end of our frequency range we achieve a worst-case upper limit of 3.8 x 10(-24) for all polarizations and sky locations. These results constitute a factor of 2 improvement upon previously published data. A new detection pipeline utilizing a loosely coherent algorithm was able to follow up weaker outliers, increasing the volume of space where signals can be detected by a factor of 10, but has not revealed any gravitational-wave signals. The pipeline has been tested for robustness with respect to deviations from the model of an isolated neutron star, such as caused by a low-mass or long-period binary companion.
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| 4. |
- Abadie, J., et al.
(författare)
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Search for Gravitational Waves Associated with Gamma-Ray Bursts during LIGO Science Run 6 and Virgo Science Runs 2 and 3
- 2012
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Ingår i: Astrophysical Journal. - 0004-637X. ; 760:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a search for gravitational waves associated with 154 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments in 2009-2010, during the sixth LIGO science run and the second and third Virgo science runs. We perform two distinct searches: a modeled search for coalescences of either two neutron stars or a neutron star and black hole, and a search for generic, unmodeled gravitational-wave bursts. We find no evidence for gravitational-wave counterparts, either with any individual GRB in this sample or with the population as a whole. For all GRBs we place lower bounds on the distance to the progenitor, under the optimistic assumption of a gravitational-wave emission energy of 10(-2) M-circle dot c(2) at 150 Hz, with a median limit of 17 Mpc. For short-hard GRBs we place exclusion distances on binary neutron star and neutron-star-black-hole progenitors, using astrophysically motivated priors on the source parameters, with median values of 16 Mpc and 28 Mpc, respectively. These distance limits, while significantly larger than for a search that is not aided by GRB satellite observations, are not large enough to expect a coincidence with a GRB. However, projecting these exclusions to the sensitivities of Advanced LIGO and Virgo, which should begin operation in 2015, we find that the detection of gravitational waves associated with GRBs will become quite possible.
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| 5. |
- Abadie, J., et al.
(författare)
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All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
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Tidskriftsartikel (refereegranskat)abstract
- We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration less than or similar to 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc(3) for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range similar to 5 x 10(-22) Hz(-1/2) to similar to 1 x 10(-20) Hz(-1/2). The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.
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| 6. |
- Abadie, J., et al.
(författare)
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First low-latency LIGO plus Virgo search for binary inspirals and their electromagnetic counterparts
- 2012
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 541
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The detection and measurement of gravitational-waves from coalescing neutron-star binary systems is an important science goal for ground-based gravitational-wave detectors. In addition to emitting gravitational-waves at frequencies that span the most sensitive bands of the LIGO and Virgo detectors, these sources are also amongst the most likely to produce an electromagnetic counterpart to the gravitational-wave emission. A joint detection of the gravitational-wave and electromagnetic signals would provide a powerful new probe for astronomy. Methods. During the period between September 19 and October 20, 2010, the first low-latency search for gravitational-waves from binary inspirals in LIGO and Virgo data was conducted. The resulting triggers were sent to electromagnetic observatories for followup. We describe the generation and processing of the low-latency gravitational-wave triggers. The results of the electromagnetic image analysis will be described elsewhere. Results. Over the course of the science run, three gravitational-wave triggers passed all of the low-latency selection cuts. Of these, one was followed up by several of our observational partners. Analysis of the gravitational-wave data leads to an estimated false alarm rate of once every 6.4 days, falling far short of the requirement for a detection based solely on gravitational-wave data.
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| 7. |
- Abadie, J., et al.
(författare)
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Search for gravitational waves from intermediate mass binary black holes
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:10
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of a weakly modeled burst search for gravitational waves from mergers of nonspinning intermediate mass black holes in the total mass range 100-450 M-circle dot and with the component mass ratios between 1: and 4:1. The search was conducted on data collected by the LIGO and Virgo detectors between November of 2005 and October of 2007. No plausible signals were observed by the search which constrains the astrophysical rates of the intermediate mass black holes mergers as a function of the component masses. In the most efficiently detected bin centered on 88 + 88 M-circle dot, for nonspinning sources, the rate density upper limit is 0.13 per Mpc(3) per Myr at the 90% confidence level.
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| 8. |
- Abadie, J., et al.
(författare)
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Upper limits on a stochastic gravitational-wave background using LIGO and Virgo interferometers at 600-1000 Hz
- 2012
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 85:12
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Tidskriftsartikel (refereegranskat)abstract
- A stochastic background of gravitational waves is expected to arise from a superposition of many incoherent sources of gravitational waves, of either cosmological or astrophysical origin. This background is a target for the current generation of ground-based detectors. In this article we present the first joint search for a stochastic background using data from the LIGO and Virgo interferometers. In a frequency band of 600-1000 Hz, we obtained a 95% upper limit on the amplitude of Omega(GW)(f) = Omega(3)(f/900 Hz)(3), of Omega(3) < 0.32, assuming a value of the Hubble parameter of h(100) = 0.71. These new limits are a factor of seven better than the previous best in this frequency band.
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| 9. |
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| 10. |
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| 11. |
- Mansoor, Rashid, et al.
(författare)
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Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
- 2022
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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| 12. |
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| 13. |
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| 14. |
- Adjuik, Martin A., et al.
(författare)
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The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria : a meta-analysis of individual patient data
- 2015
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.
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| 15. |
- Al-Khan, A., et al.
(författare)
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IFPA Meeting 2010 Workshops Report II: Placental pathology; Trophoblast invasion; Fetal sex; Parasites and the placenta; Decidua and embryonic or fetal loss; Trophoblast differentiation and syncytialisation
- 2011
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 32:Suppl. 2, s. 90-99
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. (C) 2011 Published by IFPA and Elsevier Ltd.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
- Boxall, A. B. A., et al.
(författare)
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Pharmaceuticals and Personal Care Products in the Environment: What Are the Big Questions?
- 2012
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:9, s. 1221-1229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. OBJECTIVE: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. DATA SOURCES: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. DATA SYNTHESIS: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, a effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. CONCLUSIONS: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.
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| 21. |
- Venkatesan, M, et al.
(författare)
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Erratum
- 2019
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Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 100:3, s. 766-766
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Bernatsky, S, et al.
(författare)
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An International Cohort Study of Cancer in Systemic Lupus Erythematosus
- 2005
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 52:5, s. 1481-1490
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Tidskriftsartikel (refereegranskat)abstract
- Objective. There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. Methods. We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. Results. The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). Conclusion. These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.
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| 23. |
- Bernatsky, S., et al.
(författare)
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Mortality in systemic lupus erythematosus
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 54:8, s. 2550-2557
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. Methods. Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for-all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. Results. The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration < 1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. Conclusion. Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.
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| 24. |
- Becker, J. C., et al.
(författare)
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What do national flags stand for? : An exploration of associations across 11 countries
- 2017
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Ingår i: Journal of Cross-Cultural Psychology. - : Sage Publications. - 0022-0221 .- 1552-5422. ; 48:3, s. 335-352
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Tidskriftsartikel (refereegranskat)abstract
- We examined the concepts and emotions people associate with their national flag, and how these associations are related to nationalism and patriotism across 11 countries. Factor analyses indicated that the structures of associations differed across countries in ways that reflect their idiosyncratic historical developments. Positive emotions and egalitarian concepts were associated with national flags across countries. However, notable differences between countries were found due to historical politics. In societies known for being peaceful and open-minded (e.g., Canada, Scotland), egalitarianism was separable from honor-related concepts and associated with the flag; in countries that were currently involved in struggles for independence (e.g., Scotland) and countries with an imperialist past (the United Kingdom), the flag was strongly associated with power-related concepts; in countries with a negative past (e.g., Germany), the primary association was sports; in countries with disruption due to separatist or extremist movements (e.g., Northern Ireland, Turkey), associations referring to aggression were not fully rejected; in collectivist societies (India, Singapore), obedience was linked to positive associations and strongly associated with the flag. In addition, the more strongly individuals endorsed nationalism and patriotism, the more they associated positive emotions and egalitarian concepts with their flag. Implications of these findings are discussed.
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| 25. |
- Bernatsky, Sasha, et al.
(författare)
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Cancer risk in systemic lupus: An updated international multi-centre cohort study
- 2013
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 42, s. 130-135
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To update estimates of cancer risk in SLE relative to the general population. Methods: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Results: Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% Cl 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). Conclusion: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing. (C) 2013 Elsevier Ltd. All rights reserved.
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| 26. |
- Bernatsky, S, et al.
(författare)
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Non-Hodgkin's lymphoma in systemic lupus erythematosus
- 2005
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 64:10, s. 1507-1509
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). Objectives: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. Methods: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. Results: 42 cases of NHL occurred in the patients with SLE during the 76 948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell ( 11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. Conclusions: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.
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| 27. |
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| 28. |
- Dahal, Prabin, et al.
(författare)
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Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria : a WorldWide Antimalarial Resistance Network individual participant data meta-analysis
- 2019
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Ingår i: Malaria Journal. - : BMC. - 1475-2875. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections.Methods: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model.Results: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (rho): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [rho: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold.Conclusions: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
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| 29. |
- Dahal, Prabin, et al.
(författare)
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Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
- 2022
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Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
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| 31. |
- Venkatesan, Meera, et al.
(författare)
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Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes : parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine.
- 2014
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Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 91:4, s. 833-43
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Tidskriftsartikel (refereegranskat)abstract
- Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Barragan, A, et al.
(författare)
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Transepithelial migration of Toxoplasma gondii is linked to parasite motility and virulence
- 2002
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 195:12, s. 1625-1633
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Tidskriftsartikel (refereegranskat)abstract
- After oral ingestion, Toxoplasma gondii crosses the intestinal epithelium, disseminates into the deep tissues, and traverses biological barriers such as the placenta and the blood-brain barrier to reach sites where it causes severe pathology. To examine the cellular basis of these processes, migration of T. gondii was studied in vitro using polarized host cell monolayers and extracellular matrix. Transmigration required active parasite motility and the highly virulent type I strains consistently exhibited a superior migratory capacity than the nonvirulent type II and type III strains. Type I strain parasites also demonstrated a greater capacity for transmigration across mouse intestine ex vivo, and directly penetrated into the lamina propria and vascular endothelium. A subpopulation of virulent type I parasites exhibited a long distance migration (LDM) phenotype in vitro, that was not expressed by nonvirulent type II and type III strains. Cloning of parasites expressing the LDM phenotype resulted in substantial increase of migratory capacity in vitro and in vivo. The potential to up-regulate migratory capacity in T. gondii likely plays an important role in establishing new infections and in dissemination upon reactivation of chronic infections.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Jansson, Thomas, 1955, et al.
(författare)
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Placental transport and metabolism in fetal overgrowth -- a workshop report.
- 2006
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Ingår i: Placenta. - : Elsevier BV. - 0143-4004. ; 27 Suppl A
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Tidskriftsartikel (refereegranskat)abstract
- Fetal overgrowth in pregnancies complicated by diabetes is the result of an increased substrate availability which stimulates fetal insulin secretion and fetal growth. However, despite strict glycemic control in modern clinical management of the pregnant woman with diabetes, fetal overgrowth remains an important clinical problem. Recent studies in vivo provide evidence for increased delivery of amino acids to the fetus in gestational diabetes (GDM) even when metabolic control is strict. This could be due to that truly normal maternal substrate levels cannot be achieved in diabetic pregnancies and/or caused by altered placental nutrient transport and metabolism. Studies in vitro demonstrate an up-regulation of placental transport systems for certain amino acids in GDM associated with fetal overgrowth. GDM is also characterized by changes in placental gene expression, including up-regulation of inflammatory mediators and Leptin. In type-I diabetes with fetal overgrowth the in vitro activity of placental transporters for both glucose and certain amino acids as well as placental lipoprotein lipase is increased. Furthermore, both clinical observations in type-I diabetic pregnancies and preliminary animal experimental studies suggest that even brief periods of metabolic perturbation early in pregnancy may affect placental growth and transport function for the remainder of pregnancy, thereby contributing to fetal overgrowth. Ultrasound measurements of fetal fat deposits and abdominal circumference as well as 3D ultrasound assessment of placental volume represent non-invasive techniques for in utero diagnosis of fetal and placental overgrowth. It is proposed that these methods represent valuable additions to the clinical management of the diabetic pregnancy. In conclusion, altered placental function may be a mechanism contributing to fetal overgrowth in diabetic pregnancies with apparent optimal metabolic control. It is proposed that detailed information on placental metabolism and transport functions obtained in vitro and in vivo represent a placental phenotype that provides important information and may facilitate diagnosis and improve clinical management of fetal overgrowth.
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| 40. |
- Kwon, J. Y., et al.
(författare)
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Patient-Reported Outcomes Measurement in Radiation Oncology: Interpretation of Individual Scores and Change over Time in Clinical Practice
- 2022
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Ingår i: Current Oncology. - : MDPI AG. - 1198-0052 .- 1718-7729. ; 29:5, s. 3093-3103
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Tidskriftsartikel (refereegranskat)abstract
- Tools for measuring patients' perceived health and quality of life, such as patient-reported outcome measures (PROMs), inform clinical decisions for patients requiring radiation therapy. However, there may be inconsistencies in how patients interpret and respond to PROMs due to cultural, environmental, personal, or experiential factors. Differential item functioning (DIF) and response shift (RS) refer to differences in the meaning of PROMs between patients or over time (respectively). DIF and RS can threaten the accurate interpretation and use of PROMs, potentially resulting in erroneous conclusions about effectiveness, and flawed individual-level clinical decision-making. Given the empirical evidence of DIF and RS, we aim to review clinical implications and solutions for addressing DIF and RS by providing vignettes from collaborative examinations with workshop participants, as well as the literature. By making these methodological concepts accessible and relevant, for practice, clinicians may feel more confident to ask clarifying questions of patients when PROM scores and the contextual patient information do not align. PROM scores need to be interpreted via dialogue with the patient to avoid misinterpretation due to DIF and RS, which could diminish patient-clinician communication and impede shared decision-making. This work is part of an interdisciplinary knowledge translation initiative focused on the interpretation of PROM scores by clinically-oriented audiences.
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| 41. |
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| 42. |
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| 43. |
- Sibley, C. G., et al.
(författare)
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Your sexism predicts my sexism : Perceptions of men's (but not women's) sexism affects one's own sexism over time
- 2009
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Ingår i: Sex Roles. - : Springer. - 0360-0025 .- 1573-2762. ; 60:9-10, s. 682-693
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Tidskriftsartikel (refereegranskat)abstract
- The effects of perceived normative (societal) levels of benevolent (BS) and hostile sexism (HS) on one's own sexist attitudes were examined over a four-month period in an undergraduate New Zealand sample (76 women, 26 men). Perceptions of normative levels of men's BS produced longitudinal change in one's own BS, and this effect was invariant across gender. However, contrary to previous research suggesting that women endorse BS when men are high in HS for its protective benefits, women instead expressed subjectively positive paternalistic attitudes toward their gender to the extent that they perceived BS as normative in men. The transmission of patriarchical-defined ideologies is tempered by the degree to which such ideologies espouse benevolent versus more overtly hostile attitudes toward women.
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| 44. |
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