QUantitative Imaging of eXtraction of oxygen and TIssue consumption (QUIXOTIC) using venular-targeted velocity-selective spin labeling

available in PMC 2012 December 1While oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are fundamental parameters of brain health and function, a robust MRI-based mapping of OEF and CMRO2 amenable to functional MRI (fMRI) has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from postcapillary venular blood on a voxel-by-voxel basis. Measuring the T2 of this venular-targeted blood allows calibration to venular oxygen saturation (Yv) via theoretical and experimental T2 versus blood oxygen saturation relationships. Yv is converted to OEF, and baseline CMRO2 is subsequently estimated from OEF and additional cerebral blood flow and hematocrit measurements. Theory behind the QUIXOTIC technique is presented, and implications of cutoff velocity (VCUTOFF) and outflow time parameters are discussed. Cortical gray matter values obtained with QUIXOTIC in 10 healthy volunteers are Yv = 0.73 ± 0.02, OEF = 0.26 ± 0.02, and CMRO2 = 125 ± 15 μmol/100 g min. Results are compared to global measures obtained with the T2 relaxation under spin tagging (TRUST) technique. The preliminary data presented suggest that QUIXOTIC will be useful for mapping Yv, OEF, and CMRO2, in both clinical and functional MRI settings.National Institutes of Health (U.S.) (NIH Neuroimaging Training Program Grant, 5-T32-EB001680)National Institutes of Health (U.S.) (NIH Neuroimaging Training Program Grant, 5-R01-EB002066-20)National Institutes of Health (U.S.) (Center for Functional Neuroimaging Technologies; Grant number: P41RR14075S10RR023401)Siemens Aktiengesellschaft (Siemens Medical Solutions)Harvard University--MIT Division of Health Sciences and Technology (Martinos Catalyst Fund)National Cancer Institute (U.S.) (NIH Grant number RO1 EB007942)National Institutes of Health (U.S.) (NIH Medical Scientist Training Program Fellowship, grant no. T32-GM07753

Mathematical stories: Why do more boys than girls choose to study mathematics at AS-level in England?

Copyright @ 2005 Taylor & FrancisIn this paper I address the question: How is it that people come to choose mathematics and in what ways is this process gendered? I draw on the findings of a qualitative research study involving interviews with 43 young people all studying mathematics in post-compulsory education in England. Working within a post-structuralist framework, I argue that gender is a project and one that is achieved in interaction with others. Through a detailed reading of Toni and Claudia’s stories I explore the tensions for young women who are engaging in mathematics, something that is discursively inscribed as masculine, while (understandably) being invested in producing themselves as female. I conclude by arguing that seeing ‘doing mathematics’ as ‘doing masculinity’ is a productive way of understanding why mathematics is so male dominated and by looking at the implications of this understanding for gender and mathematics reform work.This work is funded by the ESR

Genotyping of Human Lice Suggests Multiple Emergences of Body Lice from Local Head Louse Populations

While being phenotypically and physiologically different, human head and body lice are indistinguishable based on mitochondrial and nuclear genes. As protein-coding genes are too conserved to provide significant genetic diversity, we performed strain-typing of a large collection of human head and body lice using variable intergenic spacer sequences. Ninety-seven human lice were classified into ninety-six genotypes based on four intergenic spacer sequences. Genotypic and phylogenetic analyses using these sequences suggested that human head and body lice are still indistinguishable. We hypothesized that the phenotypic and physiological differences between human head and body lice are controlled by very limited mutations. Under conditions of poor hygiene, head lice can propagate very quickly. Some of them will colonize clothing, producing a body louse variant (genetic or phenetic), which can lead to an epidemic. Lice collected in Rwanda and Burundi, where outbreaks of louse-borne diseases have been recently reported, are grouped tightly into a cluster and those collected from homeless people in France were also grouped into a cluster with lice collected in French non-homeless people. Our strain-typing approach based on highly variable intergenic spacers may be helpful to elucidate louse evolution and to survey louse-borne diseases

Clinical chronobiology: a timely consideration in critical care medicine

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences and Countermeasures.

Circadian (∼ 24 hour) timing systems pervade all kingdoms of life, and temporally optimize behaviour and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behaviour and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these too are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally-driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioural and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important

Scrub typhus ecology: a systematic review of Orientia in vectors and hosts

Abstract Scrub typhus, caused by Orientia tsutsugamushi, is an important and neglected vector-borne zoonotic disease with an expanding known distribution. The ecology of the disease is complex and poorly understood, impairing discussion of public health interventions. To highlight what we know and the themes of our ignorance, we conducted a systematic review of all studies investigating the pathogen in vectors and non-human hosts. A total of 276 articles in 7 languages were included, with 793 study sites across 30 countries. There was no time restriction for article inclusion, with the oldest published in 1924. Seventy-six potential vector species and 234 vertebrate host species were tested, accounting for over one million trombiculid mites (‘chiggers’) and 83,000 vertebrates. The proportion of O. tsutsugamushi positivity was recorded for different categories of laboratory test and host species. Vector and host collection sites were geocoded and mapped. Ecological data associated with these sites were summarised. A further 145 articles encompassing general themes of scrub typhus ecology were reviewed. These topics range from the life-cycle to transmission, habitats, seasonality and human risks. Important gaps in our understanding are highlighted together with possible tools to begin to unravel these. Many of the data reported are highly variable and inconsistent and minimum data reporting standards are proposed. With more recent reports of human Orientia sp. infection in the Middle East and South America and enormous advances in research technology over recent decades, this comprehensive review provides a detailed summary of work investigating this pathogen in vectors and non-human hosts and updates current understanding of the complex ecology of scrub typhus. A better understanding of scrub typhus ecology has important relevance to ongoing research into improving diagnostics, developing vaccines and identifying useful public health interventions to reduce the burden of the disease.</jats:p