Revised NODDI model for diffusion MRI data with multiple b-tensor encodings

This work proposes a revision of the NODDI model to relate brain tissue microstructure to the new generation of diffusion MRI data with multiple b-tensor encodings. NODDI was developed originally for conventional multi-shell diffusion data acquired with linear tensor encoding (LTE). While adequate for LTE data, it has been shown to be incompatible with data using spherical tensor encoding (STE). We embed a different set of assumptions in NODDI, while retaining the tortuosity constraint, to accommodate both LTE and STE data. Experiments with human data with multiple b-tensor encodings confirm the efficacy of the revision

Blood and cerebrospinal fluid neurofilament light differentially detect neurodegeneration in early Alzheimer's disease

Cerebrospinal fluid (CSF) neurofilament light (NfL) concentration has reproducibly been shown to reflect neurodegeneration in brain disorders, including Alzheimer’s disease (AD). NfL concentration in blood correlates with the corresponding CSF levels, but few studies have directly compared the reliability of these 2 markers in sporadic AD. Herein, we measured plasma and CSF concentrations of NfL in 478 cognitively unimpaired (CU) subjects, 227 patients with mild cognitive impairment, and 113 patients with AD dementia. We found that the concentration of NfL in CSF, but not in plasma, was increased in response to Ab pathology in CU subjects. Both CSF and plasma NfL concentrations were increased in patients with mild cognitive impairment and AD dementia. Furthermore, only NfL in CSF was associated with reduced white matter microstructure in CU subjects. Finally, in a transgenic mouse model of AD, CSF NfL increased before serum NfL in response to the development of Ab pathology. In conclusion, NfL in CSF may be a more reliable biomarker of neurodegeneration than NfL in blood in preclinical sporadic AD

The effects of water and microstructure on the performance of polymer electrolyte fuel cells

n this paper, we present a comprehensive non-isothermal, one-dimensional model of the cathode side of a Polymer Electrolyte Fuel Cell. We explicitly include the catalyst layer, gas diffusion layer and the membrane. The catalyst layer and gas diffusion layer are characterized by several measurable microstructural parameters. We model all three phases of water, with a view to capturing the effect that each has on the performance of the cell. A comparison with experiment is presented, demonstrating excellent agreement, particularly with regard to the effects of water activity in the channels and how it impacts flooding and membrane hydration. We present several results pertaining to the effects of water on the current density (or cell voltage), demonstrating the role of micro-structure, liquid water removal from the channel, water activity, membrane and gas diffusion layer thickness and channel temperature. These results provide an indication of the changes that are required to achieve optimal performance through improved water management and MEA-component design. Moreover, with its level of detail, the model we develop forms an excellent basis for a multi-dimensional model of the entire membrane electrode assembly

Island properties dominate species traits in determining plant colonizations in an archipelago system

The extrinsic determinants hypothesis emphasizes the essential role of environmental heterogeneity in species' colonization. Consequently, high resident species diversity can increase community susceptibility to colonizations because good habitats may support more species that are functionally similar to colonizers. On the other hand, colonization success is also likely to depend on species traits. We tested the relative importance of environmental characteristics and species traits in determining colonization success using census data of 587 vascular plant species collected about 70 yr apart from 471 islands in the archipelago of SW Finland. More specifically, we explored potential new colonization as a function of island properties (e.g. location, area, habitat diversity, number of resident species per unit area), species traits (e.g. plant height, life-form, dispersal vector, Ellenberg indicator values, association with human impact), and species' historical distributions (number of inhabited islands, nearest occurrence). Island properties and species' historical distributions were more effective than plant traits in explaining colonization outcomes. Contrary to the extrinsic determinants hypothesis, colonization success was neither associated with resident species diversity nor habitat diversity per se, although colonization was lowest on sparsely vegetated islands. Our findings lead us to propose that while plant traits related to dispersal and establishment may enhance colonization, predictions of plant colonizations primarily require understanding of habitat properties and species' historical distributions.Peer reviewe

Ribonucleotide reductase is not limiting for mitochondrial DNA copy number in mice

Peer reviewe

A qualitative evaluation of volunteers' experiences in a phase I/II HIV vaccine trial in Tanzania

Evaluating experiences of volunteers in an HIV vaccine trial will be useful for the conduct of future trials. The purpose of this study among volunteers who participated in a phase I/II HIV vaccine trial in Dar es Salaam, Tanzania was to assess what characterized their experiences during the trial. We conducted four focus group discussions with 35 out of the 60 individuals (women and men) after the five scheduled vaccinations. An interpretive description approach was applied to data analysis. As a result of the trial interventions, both men and women gained confidence in their own abilities to have safer, less risky sexual behaviour. The participants experienced the trial as a way of accessing free [insured] medical services. Most of the men said they had gone from self-medication to professional medical consultation. Despite these benefits, the participants faced various challenges during the trial. Such challenges included mistrust of the trial shown by health care providers who were not connected to the trial and discouragement from friends, colleagues and family members who questioned the safety of the trial. However, they managed to cope with these doubts by using both personal and trial related interventions. We found that during the phase I/II HIV vaccine trial, participants had both the opportunities and the ability to cope with the doubts from the surrounding community. Follow up visits enhanced the opportunities and individuals' abilities to cope with the doubts during the trial. Understanding this discourse may be useful for the trial implementers when designing future trials.\ud \ud \ud \u

HIV-1 Superinfection in the Antiretroviral Therapy Era: Are Seroconcordant Sexual Partners at Risk?

Acquisition of more than one strain of human immunodeficiency virus type 1 (HIV-1) has been reported to occur both during and after primary infection, but the risks and repercussions of dual and superinfection are incompletely understood. In this study, we evaluated a longitudinal cohort of chronically HIV-infected men who were sexual partners to determine if individuals acquired their partners' viral strains.Our cohort of HIV-positive men consisted of 8 couples that identified themselves as long-term sexual partners. Viral sequences were isolated from each subject and analyzed using phylogenetic methods. In addition, strain-specific PCR allowed us to search for partners' viruses present at low levels. Finally, we used computational algorithms to evaluate for recombination between partners' viral strains.All couples had at least one factor associated with increased risk for acquisition of new HIV strains during the study, including detectable plasma viral load, sexually transmitted infections, and unprotected sex. One subject was dually HIV-1 infected, but neither strain corresponded to that of his partner. Three couples' sequences formed monophyletic clusters at the entry visit, with phylogenetic analysis suggesting that one member of the couple had acquired an HIV strain from his identified partner or that both had acquired it from the same source outside their partnership. The 5 remaining couples initially displayed no evidence of dual infection, using phylogenetic analysis and strain-specific PCR. However, in 1 of these couples, further analysis revealed recombinant viral strains with segments of viral genomes in one subject that may have derived from the enrolled partner. Thus, chronically HIV-1 infected individuals may become superinfected with additional HIV strains from their seroconcordant sexual partners. In some cases, HIV-1 superinfection may become apparent when recombinant viral strains are detected