| 1. |
- Geli, Patricia, et al.
(författare)
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A multi-type branching model with varying environment for bacterial dynamics with postantibiotic effect
- 2009
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Ingår i: Journal of Theoretical Biology. - : Elsevier BV. - 0022-5193 .- 1095-8541. ; 256:1, s. 58-64
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Tidskriftsartikel (refereegranskat)abstract
- A multi-type branching process with varying environment was used to construct a pharmacokinetic/pharmacodynamic (PK/PD) model that captures the postantibiotic effect (PAE) seen in bacterial populations after exposure of antibiotics. This phenomenon of continued inhibition of bacterial growth even after removal of the antibiotic from the growth medium is of high relevance in the context of optimizing dosing regimens. The clinical implication of long PAEs lies in the interesting possibility of increasing the intervals between drug administrations. The model structure is generalizable to most types of antibiotics and is useful both as a theoretical framework for understanding the time properties of PAE and to explore optimal antibiotic dosing regimens. Data from an in vitro study with Escherichia coli exposed to different dosing regimens of cefotaxime were used to evaluate the model.
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| 2. |
- Geli Rolfhamre, Patricia, 1979-
(författare)
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From Penicillin Binding Proteins to Community Interventions : Mathematical and Statistical Models Related to Antibiotic Resistance
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance has become a major public health concern and mathematical models are important analytical tools for the understanding, evaluation and prediction of the resistance problem and related control strategies.The risk of emerging antibiotic resistance and selection has rarely been a concern in the design of antibiotic drug dosing regimens. In the first paper, a selection of antibiotic resistant subpopulations for different antibiotic dosing regimens was studied in vitro. The demonstrated complex relationship was influenced by both the rise of new mutants and a postantibiotic effect (PAE) (continued inhibition of bacterial growth after removal of the antibiotic drug). By constructing a mathematical model that incorporated biologically relevant parameters, we were able to assess the risks of resistance development under different dosing strategies.In the second paper, the model for PAEs is further developed to determine the implications for different dosing regimens. The result challenges the conventional notion that long PAEs promote extended drug dosing intervals and it allows new hypotheses to be tested experimentally based on the findings from the theoretical framework.Since PAE experiments often are time-consuming and laborious, very few studies have been reporting variation for this phenomenon. In the third paper, an extension to capture the stochastic behavior of bacterial population growth under drug exposure is made. The stochastic nature of the model is also an important complement to the existing deterministic models on drug dose drug effect relationships.The last paper describes a controlled clinical intervention study aiming at determining whether the frequency of trimethoprim resistance in E. coli can be decreased by a sudden and drastic reduction in trimethoprim use. In addition to evaluating the intervention effect, the model, given estimated parameters, is also used for predicting other interesting outcomes.
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| 3. |
- Hagey, Daniel W., et al.
(författare)
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Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
- 2016
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:7, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
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| 4. |
- Andersson, Johan, 1971-
(författare)
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Summation formulae and zeta functions
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis in analytic number theory consists of 3 parts and 13 individual papers.In the first part we prove some results in Turán power sum theory. We solve a problem of Paul Erdös and disprove conjectures of Paul Turán and K. Ramachandra that would have implied important results on the Riemann zeta function.In the second part we prove some new results on moments of the Hurwitz and Lerch zeta functions (generalized versions of the Riemann zeta function) on the critical line.In the third and final part we consider the following question: What is the natural generalization of the classical Poisson summation formula from the Fourier analysis of the real line to the matrix group SL(2,R)? There are candidates in the literature such as the pre-trace formula and the Selberg trace formula.We develop a new summation formula for sums over the matrix group SL(2,Z) which we propose as a candidate for the title "The Poisson summation formula for SL(2,Z)". The summation formula allows us to express a sum over SL(2,Z) of smooth functions f on SL(2,R) with compact support, in terms of spectral theory coming from the full modular group, such as Maass wave forms, holomorphic cusp forms and the Eisenstein series. In contrast, the pre-trace formula allows us to get such a result only if we assume that f is also SO(2) bi-invariant.We indicate the summation formula's relationship with additive divisor problems and the fourth power moment of the Riemann zeta function as given by Motohashi. We prove some identities on Kloosterman sums, and generalize our main summation formula to a summation formula over integer matrices of fixed determinant D. We then deduce some consequences, such as the Kuznetsov summation formula, the Eichler-Selberg trace formula and the classical Selberg trace formula.
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| 5. |
- Andersson, Mikael, et al.
(författare)
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Interplay between the Reorientational Dynamics of the B3H8- Anion and the Structure in KB3H8
- 2021
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 125:7, s. 3716-3724
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Tidskriftsartikel (refereegranskat)abstract
- The structure and reorientational dynamics of KB3H8 were studied by using quasielastic and inelastic neutron scattering, Raman spectroscopy, first-principles calculations, differential scanning calorimetry, and in situ synchrotron radiation powder X-ray diffraction. The results reveal the existence of a previously unknown polymorph in between the alpha'- and beta-polymorphs. Furthermore, it was found that the [B3H8](-) anion undergoes different reorientational motions in the three polymorphs alpha, alpha', and beta. In alpha-KB3H8, the [B3H8](-) anion performs 3-fold rotations in the plane created by the three boron atoms, which changes to a 2-fold rotation around the C-2 symmetry axis of the [B3H8](-) anion upon transitioning to alpha'-KB3H8. After transitioning to beta-KB3H8, the [B3H8](-) anion performs 4-fold rotations in the plane created by the three boron atoms, which indicates that the local structure of beta-KB3H8 deviates from the global cubic NaCl-type structure. The results also indicate that the high reorientational mobility of the [B3H8](-) anion facilitates the K+ cation conductivity, since the 2-orders-of-magnitude increase in the anion reorientational mobility observed between 297 and 311 K coincides with a large increase in K+ conductivity.
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| 6. |
- Andersson, Mikael, 1988, et al.
(författare)
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Interplay of NH4+ and BH4- reorientational dynamics in NH4BH4
- 2020
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Ingår i: Physical Review Materials. - 2475-9953. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- The reorientational dynamics of ammonium borohydride (NH4BH4) was studied using quasielastic neutron scattering in the temperature interval from 10 to 240 K, which covers both the dynamically ordered and disordered polymorphs of NH4BH4. In the low-temperature (50 K) ordered polymorph of NH4BH4, analysis of the quasielastic neutron scattering data reveals that no reorientational dynamics is present within the probed timescale region of 0.1 to 100 ps. In the high-temperature (50 K) disordered polymorph, the analysis establishes the onset of NH4+ and BH4- dynamics at around 50 and 125 K, respectively. The relaxation time at 150 K for NH4+ is approximately 1 ps, while around 100 ps for BH4- . The NH4+ dynamics at temperatures below 125 K is associated with preferential tetrahedral tumbling motions, where each of the hydrogen atoms in the NH4+ tetrahedron can visit any of the four hydrogen sites, however, reorientations around a specific axis are more frequently occurring (C-2 or C3). At higher temperatures, the analysis does not exclude a possible evolution of the NH4+ dynamics from tetrahedral tumbling to either cubic tumbling, where the hydrogen atoms can visit any of the eight positions corresponding to the corners of a cube, or isotropic rotational diffusion, where the hydrogen atoms can visit any location on the surface of a sphere. The BH4- dynamics can be described as cubic tumbling. The difference in reorientational dynamics between the two ions is related to the difference of the local environment where the dynamically much slower BH4- anion imposes a noncubic environment on the NH4+ cation.
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| 7. |
- Andersson, Mikael, et al.
(författare)
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Modelling the spread of penicillin-resistant Streptococcus pneumoniae in day-care and evaluation of intervention.
- 2005
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Ingår i: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 24:23, s. 3593-607
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Tidskriftsartikel (refereegranskat)abstract
- In 1995, a disease control and intervention project was initiated in Malmöhus county in southern Sweden to limit the spread of penicillin-resistant pneumococci. Since most of the carriers of pneumococci are preschool children, and since most of the spread is believed to take place in day-care, a mathematical model, in the form of a stochastic process, for the spread in a day-care group was constructed. Effects of seasonal variation and size of the day-care group were particularly considered. The model was then used for comparing results from computer simulations without and with intervention. Results indicate that intervention is highly effective in day-care groups with more than ten children during the second half of the year.
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| 8. |
- Andersson, Mikael
(författare)
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The asymptotic final size distribution of multitype chain-binomial epidemic processes.
- 1999
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Ingår i: Advances in Applied Probability. - 0001-8678. ; 31:1, s. 220-234
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Tidskriftsartikel (refereegranskat)abstract
- A multitype chain-binomial epidemic process is defined for a closed finite population by sampling a simple multidimensional counting process at certain points. The final size of the epidemic is then characterized, given the counting process, as the smallest root of a non-linear system of equations. By letting the population grow, this characterization is used, in combination with a branching process approximation and a weak convergence result for the counting process, to derive the asymptotic distribution of the final size. This is done for processes with an irreducible contact structure both when the initial infection increases at the same rate as the population and when it stays fixed.
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| 9. |
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| 10. |
- Aradhya, Siddartha, et al.
(författare)
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Intermarriage and COVID-19 mortality among immigrants. A population-based cohort study from Sweden
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To evaluate the role of language proficiency and institutional awareness in explaining excess COVID-19 mortality among immigrants. Design Cohort study with follow-up between 12 March 2020 and 23 February 2021. Setting Swedish register-based study on all residents in Sweden. Participants 3 963 356 Swedish residents in co-residential unions who were 30 years of age or older and alive on 12 March 2020 and living in Sweden in December 2019. Outcome measures Cox regression models were conducted to assess the association between different constellations of immigrant-native couples (proxy for language proficiency and institutional awareness) and COVID-19 mortality and all other causes of deaths (2019 and 2020). Models were adjusted for relevant confounders. Results Compared with Swedish-Swedish couples (1.18 deaths per thousand person-years), both immigrants partnered with another immigrant and a native showed excess mortality for COVID-19 (HR 1.43; 95% CI 1.29 to 1.58 and HR 1.24; 95% CI 1.10 to 1.40, respectively), which translates to 1.37 and 1.28 deaths per thousand person-years. Moreover, similar results are found for natives partnered with an immigrant (HR 1.15; 95% CI 1.02 to 1.29), which translates to 1.29 deaths per thousand person-years. Further analysis shows that immigrants from both high-income and low-income and middle-income countries (LMIC) experience excess mortality also when partnered with a Swede. However, having a Swedish-born partner is only partially protective against COVID-19 mortality among immigrants from LMIC origins. Conclusions Language barriers and/or poor institutional awareness are not major drivers for the excess mortality from COVID-19 among immigrants. Rather, our study provides suggestive evidence that excess mortality among immigrants is explained by differential exposure to the virus.
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