Rapid turnover of effector-memory CD4(+) T cells in healthy humans

Memory T cells can be divided into central-memory (T(CM)) and effector-memory (T(EM)) cells, which differ in their functional properties. Although both subpopulations can persist long term, it is not known whether they are maintained by similar mechanisms. We used in vivo labeling with deuterated glucose to measure the turnover of CD4(+) T cells in healthy humans. The CD45R0(+)CCR7(-) T(EM) subpopulation was shown to have a rapid proliferation rate of 4.7% per day compared with 1.5% per day for CD45R0(+)CCR7(+) T(CM) cells; these values are equivalent to average intermitotic (doubling) times of 15 and 48 d, respectively. In contrast, the CD45RA(+)CCR7(+) naive CD4(+) T cell population was found to be much longer lived, being labeled at a rate of only 0.2% per day (corresponding to an intermitotic time of approximately 1 yr). These data indicate that human CD4(+) T(EM) cells constitute a short-lived cell population that requires continuous replenishment in vivo

Interaction of the Host and Viral Genome and Their Influence on HIV Disease

The course of Human Immunodeficiency Virus type 1 (HIV) infection is a dynamic interplay in which both host and viral genetic variation, among other factors, influence disease susceptibility and rate of progression. HIV set-point viral load (spVL), a key indicator of HIV disease progression, has an estimated 30% of variance attributable to common heritable effects and roughly 70% attributable to environmental factors and/or additional non-genetic factors. Genome-wide genotyping and sequencing studies have allowed for large-scale association testing studying host and viral genetic variants associated with infection and disease progression. Host genomics of HIV infection has been studied predominantly in Caucasian populations consistently identifying human leukocyte antigen (HLA) genes and C-C motif chemokine receptor 5 as key factors of HIV susceptibility and progression. However, these studies don’t fully assess all classes of genetic variation (e.g., very rare polymorphisms, copy number variants etc.) and do not inform on non-European ancestry groups. Additionally, viral sequence variability has been demonstrated to influence disease progression independently of host genetic variation. Viral sequence variation can be attributed to the rapid evolution of the virus within the host due to the selective pressure of the host immune response. As the host immune system responds to the virus, e.g., through recognition of HIV antigens, the virus is able to mitigate this response by evolving HLA-specific escape mutations. Diversity of viral genotypes has also been correlated with moderate to strong effects on CD4+ T cell decline and some studies showing weak to no correlation with spVL. There is evidence to support these viral genetic factors being heritable between individuals and the evolution of these factors having important consequences in the genetic epidemiology of HIV infection on a population level. This review will discuss the host-pathogen interaction of HIV infection, explore the importance of host and viral genetics for a better understanding of pathogenesis and identify opportunities for additional genetic studies

Vortex density spectrum of quantum turbulence

The fluctuations of the vortex density in a turbulent quantum fluid are deduced from local second-sound attenuation measurements. These measurements are performed with a micromachined open-cavity resonator inserted across a flow of turbulent He-II near 1.6 K. The power spectrum of the measured vortex line density is compatible with a (-5/3) power law. The physical interpretation, still open, is discussed.Comment: Submitted to Europhys. Let

Thermal dissipation in quantum turbulence

The microscopic mechanism of thermal dissipation in quantum turbulence has been numerically studied by solving the coupled system involving the Gross-Pitaevskii equation and the Bogoliubov-de Gennes equation. At low temperatures, the obtained dissipation does not work at scales greater than the vortex core size. However, as the temperature increases, dissipation works at large scales and it affects the vortex dynamics. We successfully obtained the mutual friction coefficients of the vortex dynamics as functions of temperature, which can be applied to the vortex dynamics in dilute Bose-Einstein condensates.Comment: 4 pages, 6 figures, submitted to AP

Kolmogorov spectrum of superfluid turbulence: numerical analysis of the Gross-Pitaevskii equation with the small scale dissipation

The energy spectrum of superfluid turbulence is studied numerically by solving the Gross-Pitaevskii equation. We introduce the dissipation term which works only in the scale smaller than the healing length, to remove short wavelength excitations which may hinder the cascade process of quantized vortices in the inertial range. The obtained energy spectrum is consistent with the Kolmogorov law.Comment: 4 pages, 4 figures and 1 table. Submitted to American Journal of Physic

A preliminary investigation to group disparate batches of licit and illicit diazepam tablets using differential scanning calorimetry

Increasing numbers of illicit and unlicensed medicines are in general circulation and regularly seized by the police and other regulatory authorities. Forensic identification of seized tablets tends to focus on visual appearance and chromatographic identification of the contained drug. This process is relatively time consuming and places a strain on forensic laboratories. It was therefore of interest to investigate the possible application of differential scanning calorimetry (DSC) as a fast and efficient tool to facilitate the identification of contained drug/s and associated tablet excipients. Sixteen different cases (Cases A to P) of diazepam tablets obtained from Police Scotland were characterised based on visual appearance (colour and manufacturers' logos), physical attributes (size, weight and hardness), drug type, drug quantity (HPLC) and thermal properties (DSC). Raw DSC data was further processed using principal component analysis (PCA) as an objective assessment of the thermograms obtained with a view to statistical grouping of different cases. Cases J/K, M/O and L/P could be paired on visual appearance and Cases B/C/E/G and J/K/L/P on tablet hardness (17–23 and 80–89 N respectively). HPLC indicated that 75% of the cases examined contained diazepam but less than half of these contained the recognised amount (10 mg); Cases B/E/L/P contained phenazepam and J/K contained etizolam. The thermal signatures of individual tablets provided by DSC produced qualitative information about both drugs and excipients, indicating lactose in Cases D/F/H/I/J/K/M/N/O and Emcompress™ in B/E/L/P. In particular, DSC coupled with PCA provided confident groupings of A/C/G, B/E/L/P and H/I/J/K, and specific pairings of B/E, L/P and F/N

Neighbourhood characteristics, lifestyle factors, and child development: Secondary analysis of the All our families cohort study

BackgroundNeighbourhood characteristics have been found to influence child development, but little is known about lifestyle factors that may moderate this relationship, which can provide modifiable targets for policies and programing. This study investigated the association between neighbourhood characteristics (e.g., deprivation, disorder) during pregnancy and child development at age 5 in relation to various lifestyle factors (e.g., physical activity, parent-child reading, community resource use) during early childhood.MethodsA secondary analysis was conducted using multilevel modeling of data from the All Our Families cohort, recruited in Canada from 2008 to 2010. Participants self-reported on demographics during pregnancy, lifestyle factors at 3 years, and child development at 5 years using the Ages and Stages Questionnaire (ASQ-3). Neighbourhood deprivation was evaluated using the Vancouver Area Deprivation Index (VANDIX), while disorder was measured using police services' community crime reports.ResultsGeocoded information was available for 2,444 participants. After adjusting for covariates, multilevel modeling indicated a significant negative association between neighbourhood deprivation and overall child development (b = −.726, 95% CI: −1.344, −.120). Parent-child reading was found to be a significant moderator of the effect of neighbourhood disorder (b = .005, 95% CI: .001, .009). There were no statistically significant moderation effects for physical activity or community resource use.ConclusionNeighbourhood deprivation during pregnancy is associated with early child development. Parent-child reading may function as a protective factor in the presence of higher neighbourhood disorder. Overall, neighbourhood-level effects should be considered in policies and community programs that promote family and child well-being

Educating for urban sustainability: A transdisciplinary approach

An understanding of sustainability issues should be a key component of degree programmes. It is widely regarded as being a central attribute to professional practice and responsible global citizenship, arguably more so for the training of teachers since they potentially influence their students. This issue was brought to the fore when responsibility for delivering the 'design and the environment' course was transferred to the building discipline at the University of Newcastle in Australia as a result of restructuring. The attractiveness of the subject as an elective, the need to make it accessible to distance learning students and the desirability of applying transdisciplinary approaches to solving environmental problems presented the course designers with both challenges and opportunities, particularly in devising an assessment context within which students from multiple disciplines could be exposed to, and learn from each other's professional environmental evaluation norms. This paper describes an innovative holistic, multi-criteria problem-solving course design that allows a diverse mix of undergraduates to develop a transdisciplinary understanding of sustainability issues through the use of learning contracts. It reports the experiences of staff and students involved with the course, highlighting the beneficial outcomes

Dynamics of vortex tangle without mutual friction in superfluid 4^4He

A recent experiment has shown that a tangle of quantized vortices in superfluid $^4$He decayed even at mK temperatures where the normal fluid was negligible and no mutual friction worked. Motivated by this experiment, this work studies numerically the dynamics of the vortex tangle without the mutual friction, thus showing that a self-similar cascade process, whereby large vortex loops break up to smaller ones, proceeds in the vortex tangle and is closely related with its free decay. This cascade process which may be covered with the mutual friction at higher temperatures is just the one at zero temperature Feynman proposed long ago. The full Biot-Savart calculation is made for dilute vortices, while the localized induction approximation is used for a dense tangle. The former finds the elementary scenario: the reconnection of the vortices excites vortex waves along them and makes them kinked, which could be suppressed if the mutual friction worked. The kinked parts reconnect with the vortex they belong to, dividing into small loops. The latter simulation under the localized induction approximation shows that such cascade process actually proceeds self-similarly in a dense tangle and continues to make small vortices. Considering that the vortices of the interatomic size no longer keep the picture of vortex, the cascade process leads to the decay of the vortex line density. The presence of the cascade process is supported also by investigating the classification of the reconnection type and the size distribution of vortices. The decay of the vortex line density is consistent with the solution of the Vinen's equation which was originally derived on the basis of the idea of homogeneous turbulence with the cascade process. The obtained result is compared with the recent Vinen's theory.Comment: 16 pages, 16 figures, submitted to PR

Has education lost sight of children?

The reflections presented in this chapter are informed by clinical and personal experiences of school education in the UK. There are many challenges for children and young people in the modern education system and for the professionals who support them. In the UK, there are significant gaps between the highly selective education provided to those who pay privately for it and to the majority of those educated in the state-funded system. Though literacy rates have improved around the world, many children, particularly boys, do not finish their education for reasons such as boredom, behavioural difficulties or because education does not ‘pay’. Violence, bullying, and sexual harassment are issues faced by many children in schools and there are disturbing trends of excluding children who present with behavioural problems at school whose origins are not explored. Excluded children are then educated with other children who may also have multiple problems which often just make the situation worse. The experience of clinicians suggests that school-related mental health problems are increasing in severity. Are mental health services dealing with the consequences of an education system that is not meeting children’s needs? An education system that is testing- and performance-based may not be serving many children well if it is driving important decisions about them at increasingly younger ages. Labelling of children and setting them on educational career paths can occur well before they reach secondary schools, limiting potential very early on in their developmental trajectory. Furthermore, the emphasis at school on testing may come at the expense of creativity and other forms of intelligence, which are also valuable and important. Meanwhile the employment marketplace requires people with widely different skills, with an emphasis on innovation, creativity, and problem solving. Is education losing sight of the children it is educating