Quasi-diffusion magnetic resonance imaging (QDI): A fast, high b-value diffusion imaging technique.

To enable application of non-Gaussian diffusion magnetic resonance imaging (dMRI) techniques in large-scale clinical trials and facilitate translation to clinical practice there is a requirement for fast, high contrast, techniques that are sensitive to changes in tissue structure which provide diagnostic signatures at the early stages of disease. Here we describe a new way to compress the acquisition of multi-shell b-value diffusion data, Quasi-Diffusion MRI (QDI), which provides a probe of subvoxel tissue complexity using short acquisition times (1-4 min). We also describe a coherent framework for multi-directional diffusion gradient acquisition and data processing that allows computation of rotationally invariant quasi-diffusion tensor imaging (QDTI) maps. QDI is a quantitative technique that is based on a special case of the Continuous Time Random Walk model of diffusion dynamics and assumes the presence of non-Gaussian diffusion properties within tissue microstructure. QDI parameterises the diffusion signal attenuation according to the rate of decay (i.e. diffusion coefficient, D in mm2 s-1) and the shape of the power law tail (i.e. the fractional exponent, α). QDI provides analogous tissue contrast to Diffusional Kurtosis Imaging (DKI) by calculation of normalised entropy of the parameterised diffusion signal decay curve, Hn, but does so without the limitations of a maximum b-value. We show that QDI generates images with superior tissue contrast to conventional diffusion imaging within clinically acceptable acquisition times of between 84 and 228 s. We show that QDI provides clinically meaningful images in cerebral small vessel disease and brain tumour case studies. Our initial findings suggest that QDI may be added to routine conventional dMRI acquisitions allowing simple application in clinical trials and translation to the clinical arena

A Self-Reference False Memory Effect in the DRM Paradigm: Evidence from Eastern and Western Samples

It is well established that processing information in relation to oneself (i.e., selfreferencing) leads to better memory for that information than processing that same information in relation to others (i.e., other-referencing). However, it is unknown whether self-referencing also leads to more false memories than other-referencing. In the current two experiments with European and East Asian samples, we presented participants the Deese-Roediger/McDermott (DRM) lists together with their own name or other people’s name (i.e., “Trump” in Experiment 1 and “Li Ming” in Experiment 2). We found consistent results across the two experiments; that is, in the self-reference condition, participants had higher true and false memory rates compared to those in the other-reference condition. Moreover, we found that selfreferencing did not exhibit superior mnemonic advantage in terms of net accuracy compared to other-referencing and neutral conditions. These findings are discussed in terms of theoretical frameworks such as spreading activation theories and the fuzzytrace theory. We propose that our results reflect the adaptive nature of memory in the sense that cognitive processes that increase mnemonic efficiency may also increase susceptibility to associative false memories

Use of mixed methods designs in substance research: a methodological necessity in Nigeria

The utility of mixed methods (qualitative and quantitative) is becoming increasingly accepted in health sciences, but substance studies are yet to substantially benefit from such utilities. While there is a growing number of mixed methods alcohol articles concerning developed countries, developing nations are yet to embrace this method. In the Nigerian context, the importance of mixed methods research is yet to be acknowledged. This article therefore, draws on alcohol studies to argue that mixed methods designs will better equip scholars to understand, explore, describe and explain why alcohol consumption and its related problems are increasing in Nigeria. It argues that as motives for consuming alcohol in contemporary Nigeria are multiple, complex and evolving, mixed method approaches that provide multiple pathways for proffering solutions to problems should be embraced

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence

OBJECTIVE: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness and the acute BP response to exercise in a large birth cohort of adolescents. METHODS: 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8±0.4 years, 38.5% male) completed a submaximal exercise step-test that allowed fitness (VO2 max ) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. RESULTS: Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, height, smoking and socioeconomic status (standardized β: -1.80, 95%CI: -2.64, -0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). CONCLUSION: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realised with more-favourable body composition

Do Changes in the Pace of Events Affect One-Off Judgments of Duration?

Five experiments examined whether changes in the pace of external events influence people’s judgments of duration. In Experiments 1a–1c, participants heard pieces of music whose tempo accelerated, decelerated, or remained constant. In Experiment 2, participants completed a visuo-motor task in which the rate of stimulus presentation accelerated, decelerated, or remained constant. In Experiment 3, participants completed a reading task in which facts appeared on-screen at accelerating, decelerating, or constant rates. In all experiments, the physical duration of the to-be-judged interval was the same across conditions. We found no significant effects of temporal structure on duration judgments in any of the experiments, either when participants knew that a time estimate would be required (prospective judgments) or when they did not (retrospective judgments). These results provide a starting point for the investigation of how temporal structure affects one-off judgments of duration like those typically made in natural settings

The Mathematics of Quasi-Diffusion Magnetic Resonance Imaging

Quasi-diffusion imaging (QDI) is a novel quantitative diffusion magnetic resonance imaging (dMRI) technique that enables high quality tissue microstructural imaging in a clinically feasible acquisition time. QDI is derived from a special case of the continuous time random walk (CTRW) model of diffusion dynamics and assumes water diffusion is locally Gaussian within tissue microstructure. By assuming a Gaussian scaling relationship between temporal (α) and spatial (β) fractional exponents, the dMRI signal attenuation is expressed according to a diffusion coefficient, D (in mm2 s−1), and a fractional exponent, α. Here we investigate the mathematical properties of the QDI signal and its interpretation within the quasi-diffusion model. Firstly, the QDI equation is derived and its power law behaviour described. Secondly, we derive a probability distribution of underlying Fickian diffusion coefficients via the inverse Laplace transform. We then describe the functional form of the quasi-diffusion propagator, and apply this to dMRI of the human brain to perform mean apparent propagator imaging. QDI is currently unique in tissue microstructural imaging as it provides a simple form for the inverse Laplace transform and diffusion propagator directly from its representation of the dMRI signal. This study shows the potential of QDI as a promising new model-based dMRI technique with significant scope for further development

Quasi-Diffusion Imaging: Application to ultra-high b-value and time-dependent diffusion images of brain tissue

We demonstrate that quasi-diffusion imaging (QDI) is a signal representation that extends towards the negative power law regime. We evaluate QDI for in vivo human and ex vivo fixed rat brain tissue across b -value ranges from 0 to 25,000 s mm-2, determine whether accurate parameter estimates can be acquired from clinically feasible scan times and investigate their diffusion time-dependence. Several mathematical properties of the QDI representation are presented. QDI describes diffusion magnetic resonance imaging (dMRI) signal attenuation by two fitting parameters within a Mittag-Leffler function (MLF). We present its asymptotic properties at low and high b -values and define the inflection point (IP) above which the signal tends to a negative power law. To show that QDI provides an accurate representation of dMRI signal, we apply it to two human brain datasets (Dataset 1: 0≤b≤15,000 s mm-2; Dataset 2: 0≤b≤17,800 s mm-2) and an ex vivo fixed rat brain (Dataset 3: 0≤b≤25,000 s mm-2, diffusion times 17.5≤Δ≤200 ms). A clinically feasible 4 b -value subset of Dataset 1 ( 0≤b≤15,000 s mm-2) is also analysed (acquisition time 6 min and 16 s). QDI showed excellent fits to observed signal attenuation, identified signal IPs and provided an apparent negative power law. Stable parameter estimates were identified upon increasing the maximum b -value of the fitting range to near and above signal IPs, suggesting QDI is a valid signal representation within in vivo and ex vivo brain tissue across large b -value ranges with multiple diffusion times. QDI parameters were accurately estimated from clinically feasible shorter data acquisition, and time-dependence was observed with parameters approaching a Gaussian tortuosity limit with increasing diffusion time. In conclusion, QDI provides a parsimonious representation of dMRI signal attenuation in brain tissue that is sensitive to tissue microstructural heterogeneity and cell membrane permeability