| 1. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 2. |
- Angelopoulos, Michael, et al.
(författare)
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Deciphering the Properties of Different Arctic Ice Types During the Growth Phase of MOSAiC: Implications for Future Studies on Gas Pathways
- 2022
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Ingår i: Frontiers in Earth Science. - : Frontiers Media SA. - 2296-6463. ; 10, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- The increased fraction of first year ice (FYI) at the expense of old ice (second-year ice (SYI) and multi-year ice (MYI)) likely affects the permeability of the Arctic ice cover. This in turn influences the pathways of gases circulating therein and the exchange at interfaces with the atmosphere and ocean. We present sea ice temperature and salinity time series from different ice types relevant to temporal development of sea ice permeability and brine drainage efficiency from freeze-up in October to the onset of spring warming in May. Our study is based on a dataset collected during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) Expedition in 2019 and 2020. These physical properties were used to derive sea ice permeability and Rayleigh numbers. The main sites included FYI and SYI. The latter was composed of an upper layer of residual ice that had desalinated but survived the previous summer melt and became SYI. Below this ice a layer of new first-year ice formed. As the layer of new first-year ice has no direct contact with the atmosphere, we call it insulated first-year ice (IFYI). The residual/SYI-layer also contained refrozen melt ponds in some areas. During the freezing season, the residual/SYI-layer was consistently impermeable, acting as barrier for gas exchange between the atmosphere and ocean. While both FYI and SYI temperatures responded similarly to atmospheric warming events, SYI was more resilient to brine volume fraction changes because of its low salinity (< 2). Furthermore, later bottom ice growth during spring warming was observed for SYI in comparison to FYI. The projected increase in the fraction of more permeable FYI in autumn and spring in the coming decades may favor gas exchange at the atmosphere-ice interface when sea ice acts as a source relative to the atmosphere. While the areal extent of old ice is decreasing, so is its thickness at the onset of freeze-up. Our study sets the foundation for studies on gas dynamics within the ice column and the gas exchange at both ice interfaces, i.e. with the atmosphere and the ocean.
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| 3. |
- Becker, Richard C., et al.
(författare)
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Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban-an oral, direct and selective factor Xa inhibitor
- 2011
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 32:2, s. 183-187
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Tidskriftsartikel (refereegranskat)abstract
- An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. Anti-Xa activity, determined by either anti-Xa-LMWH (r = 0.9671; P < 0.0001) or anti-Xa-apixaban (r = 0.9669; P < 0.0001) correlated strongly and in a linear fashion with apixaban plasma concentrations. The correlations for each method were equally strong at low (< 100 ng/ml) (r = 0.86, P < 0.0001; r = 0.85, P < 0.0001), intermediate(100-200 ng/ml) (r = 0.73, P < 0.0001; r = 0.69, P < 0.0001) and high (> 200 ng/ml) (r = 0.91, P < 0.0001; r = 0.91, P < 0.0001) plasma concentrations of apixaban, respectively. Our pharmacokinetic and pharmacodynamic substudy suggests that an apixaban-mediated anticoagulant effect can be detected even at very low plasma concentrations using a standard laboratory chromogenic anti-Xa assay with either LMWH or apixaban calibrators. While establishing parameters for safety and efficacy will require further investigation, an ability to discern the presence of a drug effect may provide clinically useful information.
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| 4. |
- Becker, Richard C., et al.
(författare)
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Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome
- 2010
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 104:5, s. 976-983
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Tidskriftsartikel (refereegranskat)abstract
- Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS) Apixaban's effect on D dimer and prothrombin fragment 12 (F1 2) (coagulation activity biomarkers) was determined in a randomised, double blinded, placebo controlled phase 2 study Patients (n=1,715) with either ST segment elevation or non ST segment elevation ACS received either placebo or apixaban 2 5 mg twice daily 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months Samples were obtained at baseline (before study drug administration), week 3 and week 26 Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry and anti Xa activity was determined using apixaban as a reference standard D dimer and F 1 2 were measured using ELISA based methods Most patients had elevated D dimer and Fl 2 levels at baseline Both coagulation activity biomarkers decreased by week 3 in all treatment groups but to a greater degree with apixaban than placebo (p<0 001) In a multivariable analysis, apixaban was independently associated with a change in biomarkers over time (p<0 0001) While the overall decrease did not differ significantly among the three highest apixaban doses, Fl 2 was suppressed more rapidly by the 10 mg once daily than the 2 5 mg twice daily dose (p<0 05) There was a strong and direct relationship between apixaban plasma concentrations and anti Xa apixaban levels, and an inverse relationship for both measures with coagulation activity biomarkers In conclusion the oral direct factor Xa inhibitor apixaban significantly reduced coagulation activity biomarkers among patients with ACS The 10 mg once daily dose reduced thrombin generation (F 1 2) and fibrin formation (D dimer) more rapidly and robustly than the 25 mg twice daily dose The effect on both D dimer and F 12 was apixaban concentration and factor Xa inhibition dependent durable and provided general guidance for dose selection in phase 3 investigation.
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| 5. |
- Fang, Lanyan, et al.
(författare)
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Model-Informed Drug Development and Review for Generic Products : Summary Of FDA Public Workshop
- 2018
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Ingår i: Clinical Pharmacology and Therapeutics. - : Wiley. - 0009-9236 .- 1532-6535. ; 104:1, s. 27-30
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Tidskriftsartikel (refereegranskat)abstract
- On October 2nd and 3rd, 2017, the US Food and Drug Administration (FDA) hosted a public workshop titled “Leveraging Quantitative Methods and Modeling to Modernize Generic Drug Development and Review.”1 This report summarizes Session 2 of the public workshop: “Model Informed Drug Development and Review for Generic Products.” The session focused on the application of quantitative methods and modeling in modernizing the generic drug development and review.
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| 6. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 7. |
- Kilburn, Kelly N., et al.
(författare)
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Conditional cash transfers and the reduction in partner violence for young women : an investigation of causal pathways using evidence from a randomized experiment in South Africa (HPTN 068)
- 2018
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Ingår i: Journal of the International AIDS Society. - : JOHN WILEY & SONS LTD. - 1758-2652. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionEvidence has shown that the experience of violence by a partner has important influences on women's risk of HIV acquisition. Using a randomized experiment in northeast South Africa, we found that a conditional cash transfer (CCT) targeted to poor girls in high school reduced the risk of physical intimate partner violence (IPV) in the past 12months by 34%. The purpose of this analysis is to understand the pathways through which the CCT affects IPV. MethodsHPTN 068 was a phase 3, randomized controlled trial in rural Mpumalanga province, South Africa. Eligible young women (aged 13-20) and their parents or guardians were randomly assigned (1:1) to either receive a monthly cash transfer conditional on monthly high school attendance or no cash transfer. Between 2011 and 2015, participants (N=2,448) were interviewed at baseline, then at annual follow-up visits at 12, 24 and 36months. The total effect of the CCT on IPV was estimated using a GEE log-binomial regression model. We then estimated controlled direct effects to examine mediation of direct effects through intermediate pathways. Mediators include sexual partnership measures, the sexual relationship power scale, and household consumption measures. ResultsWe found evidence that the CCT works in part through delaying sexual debut or reducing the number of sexual partners. The intervention interacts with these mediators leading to larger reductions in IPV risk compared to the total effect of the CCT on any physical IPV [RR 0.66, CI(95%):0.59-0.74]. The largest reductions are seen when we estimate the controlled direct effect under no sexual debut [RR 0.57, CI(95%):0.48-0.65] or under no sexual partner in the last 12months [RR 0.53, CI(95%):0.46-0.60]. ConclusionsResults indicate that a CCT for high school girls has protective effects on their experience of IPV and that the effect is due in part to girls choosing not to engage in sexual partnerships, thereby reducing the opportunity for IPV. As a lower exposure to IPV and safer sexual behaviours also protect against HIV acquisition, this study adds to the growing body of evidence on how cash transfers may reduce young women's HIV risk.
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| 8. |
- Stoner, Marie C. D., et al.
(författare)
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Does Partner Selection Mediate the Relationship Between School Attendance and HIV/Herpes Simplex Virus-2 Among Adolescent Girls and Young Women in South Africa : An Analysis of HIV Prevention Trials Network 068 Data
- 2018
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Lippincott Williams & Wilkins. - 1525-4135 .- 1944-7884. ; 79:1, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Objective: School attendance prevents HIV and herpes simplex virus-2 (HSV-2) in adolescent girls and young women, but the mechanisms to explain this relationship remain unclear. Our study assesses the extent to which characteristics of sex partners, partner age, and number mediate the relationship between attendance and risk of infection in adolescent girls and young women in South Africa.Design: We use longitudinal data from the HIV Prevention Trials Network 068 randomized controlled trial in rural South Africa, where girls were enrolled in early adolescence and followed in the main trial for more than 3 years. We examined older partners and the number of partners as possible mediators.Methods: We used the parametric g-formula to estimate 4-year risk differences for the effect of school attendance on the cumulative incidence of HIV/HSV-2 overall and the controlled direct effect (CDE) for mediation. We examined mediation separately and jointly for the mediators of interest.Results: We found that young women with high attendance in school had a lower cumulative incidence of HIV compared with those with low attendance (risk difference = -1.6%). Partner age difference (CDE = -1.2%) and the number of partners (CDE = -0.4%) mediated a large portion of this effect. In fact, when we accounted for the mediators jointly, the effect of schooling on HIV was almost removed, showing full mediation (CDE = -0.3%). The same patterns were observed for the relationship between school attendance and cumulative incidence of HSV-2 infection.Conclusion: Increasing school attendance reduces the risk of acquiring HIV and HSV-2. Our results indicate the importance of school attendance in reducing partner number and partner age difference in this relationship.
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| 9. |
- Stoner, Marie C. D., et al.
(författare)
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Effect of schooling on age-disparate relationships and number of sexual partners among young women in rural South Africa enrolled in HPTN 068
- 2017
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Wolters Kluwer Health. - 1525-4135 .- 1944-7884. ; 76:5, s. E107-E114
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attending school may have a strong preventative association with sexually transmitted infections among young women, but the mechanism for this relationship is unknown. One hypothesis is that students who attend school practice safer sex with fewer partners, establishing safer sexual networks that make them less exposed to infection.Setting: We used longitudinal data from a randomized controlled trial of young women aged 13-20 years in the Bushbuckridge district, South Africa, to determine whether the percentage of school days attended, school dropout, and grade repetition are associated with having a partner 5 or more years older (age-disparate) and with the number of sexual partners in the previous 12 months.Methods: Risks of having an age-disparate relationship and number of sexual partners were compared using inverse probability of exposure weighted Poisson regression models. Generalized estimating equations were used to account for repeated measures.Results: Young women who attended fewer school days (<80%) and who dropped out of school were more likely to have an age-disparate relationship (risk difference 9.9%, 95% confidence interval [CI]: 3.9% to 16.0%; risk difference (%) dropout 17.2%, 95% CI: 5.4% to 29.0%) and those who dropped out reported having fewer partners (count difference dropout 0.343, 95% CI: 0.192 to 0.495). Grade repetition was not associated with either behavior.Conclusion: Young women who less frequently attend school or who drop out are more likely to have an age-disparate relationship. Young women who drop out have overall more partners. These behaviors may increase the risk of exposure to HIV infection in young women out of school.
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| 10. |
- Stoner, Marie C. D., et al.
(författare)
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The effect of school attendance and school dropout on incident HIV and HSV-2 among young women in rural South Africa enrolled in HPTN 068
- 2017
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Ingår i: AIDS. - : LIPPINCOTT WILLIAMS & WILKINS. - 0269-9370 .- 1473-5571. ; 31:15, s. 2127-2134
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the association between school attendance, school dropout, and risk of incident HIV and herpes simplex virus type 2 (HSV-2) infection among young women.Design: We used longitudinal data from a randomized controlled trial in rural Mpumalanga province, South Africa, to assess the association between school days attended, school dropout, and incident HIV and HSV-2 in young women aged 13-23 years.Methods: We examined inverse probability of exposure weighted survival curves and used them to calculate 1.5, 2.5, and 3.5-year risk differences and risk ratios for the effect of school attendance on incident HIV and HSV-2. A marginal structural Cox model was used to estimate hazard ratios for the effect of school attendance and school dropout on incident infection.Results: Risk of infection increased over time as young women aged, and was higher in young women with low school attendance (<80% school days) compared with high (>= 80% school days). Young women with low attendance were more likely to acquire HIV [hazard ratio (HR): 2.97; 95% confidence interval (CI): 1.62, 5.45] and HSV-2 (HR: 2.47; 95% CI: 1.46, 4.17) over the follow-up period than young women with high attendance. Similarly, young women who dropped out of school had a higher weighted hazard of both HIV (HR 3.25 95% CI: 1.67, 6.32) and HSV-2 (HR 2.70; 95% CI 1.59, 4.59).Conclusion: Young women who attend more school days and stay in school have a lower risk of incident HIV and HSV-2 infection. Interventions to increase frequency of school attendance and prevent dropout should be promoted to reduce risk of infection.
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