Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: Changes in the white matter of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) have been reported using diffusion weighted MRI, though few longitudinal studies have been done. METHODS: We performed diffusion weighted MRI twice, a year apart on 23 AD, 14 DLB, and 32 healthy control subjects. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated. RESULTS: In AD, there were widespread regions where the longitudinal MD increase was greater than in controls, and small areas in the parietal and temporal lobes where it was greater in AD than DLB. In AD, decrease in brain volume correlated with increased MD. There were no significant differences in progression between DLB and controls. CONCLUSIONS: In AD the white matter continues to degenerate during the disease process, whereas in DLB, changes in the white matter structure are a relatively early feature. Different mechanisms are likely to underpin changes in diffusivity.The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.parkreldis.2016.01.00

Using Markov Models and Statistics to Learn, Extract, Fuse, and Detect Patterns in Raw Data

Many systems are partially stochastic in nature. We have derived data driven approaches for extracting stochastic state machines (Markov models) directly from observed data. This chapter provides an overview of our approach with numerous practical applications. We have used this approach for inferring shipping patterns, exploiting computer system side-channel information, and detecting botnet activities. For contrast, we include a related data-driven statistical inferencing approach that detects and localizes radiation sources.Comment: Accepted by 2017 International Symposium on Sensor Networks, Systems and Securit

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus

BACKGROUND. Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum–filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D). METHODS. We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 μm in-plane resolution 1H MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, 23Na TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples. RESULTS. Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity. CONCLUSION. We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal “third space repository” for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium

The Molecular Biogeography of the Indo-Pacific: Testing Hypotheses With Multispecies Genetic Patterns

Aim: To test hypothesized biogeographic partitions of the tropical Indo-Pacific Ocean with phylogeographic data from 56 taxa, and to evaluate the strength and nature of barriers emerging from this test. \u3eLocation: The Indo-Pacific Ocean. Time Period: Pliocene through the Holocene. Major Taxa Studied: Fifty-six marine species. Methods: We tested eight biogeographic hypotheses for partitioning of the Indo-Pacific using a novel modification to analysis of molecular variance. Putative barriers to gene flow emerging from this analysis were evaluated for pairwise ΦST, and these ΦST distributions were compared to distributions from randomized datasets and simple coalescent simulations of vicariance arising from the Last Glacial Maximum. We then weighed the relative contribution of distance versus environmental or geographic barriers to pairwise ΦST with a distance-based redundancy analysis (dbRDA). Results: We observed a diversity of outcomes, although the majority of species fit a few broad biogeographic regions. Repeated coalescent simulation of a simple vicariance model yielded a wide distribution of pairwise ΦST that was very similar to empirical distributions observed across five putative barriers to gene flow. Three of these barriers had median ΦST that were significantly larger than random expectation. Only 21 of 52 species analysed with dbRDA rejected the null model. Among these, 15 had overwater distance as a significant predictor of pairwise ΦST, while 11 were significant for geographic or environmental barriers other than distance. Main Conclusions: Although there is support for three previously described barriers, phylogeographic discordance in the Indo-Pacific Ocean indicates incongruity between processes shaping the distributions of diversity at the species and population levels. Among the many possible causes of this incongruity, genetic drift provides the most compelling explanation: given massive effective population sizes of Indo-Pacific species, even hard vicariance for tens of thousands of years can yield ΦST values that range from 0 to nearly 0.5

The molecular biogeography of the Indo‐Pacific: Testing hypotheses with multispecies genetic patterns

Aim: To test hypothesized biogeographic partitions of the tropical Indo‐Pacific Ocean with phylogeographic data from 56 taxa, and to evaluate the strength and nature of barriers emerging from this test. Location: The Indo‐Pacific Ocean. Time period: Pliocene through the Holocene. Major taxa studied: Fifty‐six marine species. Methods: We tested eight biogeographic hypotheses for partitioning of the Indo‐ Pacific using a novel modification to analysis of molecular variance. Putative barriers to gene flow emerging from this analysis were evaluated for pairwise ΦST, and these ΦST distributions were compared to distributions from randomized datasets and simple coalescent simulations of vicariance arising from the Last Glacial Maximum. We then weighed the relative contribution of distance versus environmental or geographic barriers to pairwise ΦST with a distance‐based redundancy analysis (dbRDA). Results: We observed a diversity of outcomes, although the majority of species fit a few broad biogeographic regions. Repeated coalescent simulation of a simple vicariance model yielded a wide distribution of pairwise ΦST that was very similar to empirical distributions observed across five putative barriers to gene flow. Three of these barriers had median ΦST that were significantly larger than random expectation. Only 21 of 52 species analysed with dbRDA rejected the null model. Among these, 15 had overwater distance as a significant predictor of pairwise ΦST, while 11 were significant for geographic or environmental barriers other than distance. Main conclusions: Although there is support for three previously described barriers, phylogeographic discordance in the Indo‐Pacific Ocean indicates incongruity between processes shaping the distributions of diversity at the species and population levels. Among the many possible causes of this incongruity, genetic drift provides the most compelling explanation: given massive effective population sizes of Indo‐Pacific species, even hard vicariance for tens of thousands of years can yield ΦST values that range from 0 to nearly 0.5

QuantCrit: education, policy, ‘Big Data’ and principles for a critical race theory of statistics

Quantitative research enjoys heightened esteem among policy-makers, media and the general public. Whereas qualitative research is frequently dismissed as subjective and impressionistic, statistics are often assumed to be objective and factual. We argue that these distinctions are wholly false; quantitative data is no less socially constructed than any other form of research material. The first part of the paper presents a conceptual critique of the field with empirical examples that expose and challenge hidden assumptions that frequently encode racist perspectives beneath the façade of supposed quantitative objectivity. The second part of the paper draws on the tenets of Critical Race Theory (CRT) to set out some principles to guide the future use and analysis of quantitative data. These ‘QuantCrit’ ideas concern (1) the centrality of racism as a complex and deeply-rooted aspect of society that is not readily amenable to quantification; (2) numbers are not neutral and should be interrogated for their role in promoting deficit analyses that serve White racial interests; (3) categories are neither ‘natural’ nor given and so the units and forms of analysis must be critically evaluated; (4) voice and insight are vital: data cannot ‘speak for itself’ and critical analyses should be informed by the experiential knowledge of marginalized groups; (5) statistical analyses have no inherent value but can play a role in struggles for social justice

Coordinated and Cohesive Movement of Two Small Conspecific Fish Induced by Eliciting a Simultaneous Optomotor Response

BACKGROUND: In animal groups such as herds, schools, and flocks, a certain distance is maintained between adjacent individuals, allowing them to move as a cohesive unit. Proximate causations of the cohesive and coordinated movement under dynamic conditions, however, have been poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We established a novel and simple behavioral assay using pairs of small fish (medaka and dwarf pufferfish) by eliciting a simultaneous optomotor response (OMR). We demonstrated that two homospecific fish began to move cohesively and maintained a distance of 2 to 4 cm between them when an OMR was elicited simultaneously in the fish. The coordinated and cohesive movement was not exhibited under a static condition. During the cohesive movement, the relative position of the two fish was not stable. Furthermore, adult medaka exhibited the cohesive movement but larvae did not, despite the fact that an OMR could be elicited in larvae, indicating that this ability to coordinate movement develops during maturation. The cohesive movement was detected in homospecific pairs irrespective of body-color, sex, or albino mutation, but was not detected between heterospecific pairs, suggesting that coordinated movement is based on a conspecific interaction. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that coordinated behavior between a pair of animals was elicited by a simultaneous OMR in two small fish. This is the first report to demonstrate induction of a schooling-like movement in a pair of fish by an OMR and to investigate the effect of age, sex, body color, and species on coordination between animals under a dynamic condition

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO