Memory Inflation during Chronic Viral Infection Is Maintained by Continuous Production of Short-Lived, Functional T Cells

SummaryDuring persistent murine cytomegalovirus (MCMV) infection, the T cell response is maintained at extremely high intensity for the life of the host. These cells closely resemble human CMV-specific cells, which compose a major component of the peripheral T cell compartment in most people. Despite a phenotype that suggests extensive antigen-driven differentiation, MCMV-specific T cells remain functional and respond vigorously to viral challenge. We hypothesized that a low rate of antigen-driven proliferation would account for the maintenance of this population. Instead, we found that most of these cells divided only sporadically in chronically infected hosts and had a short half-life in circulation. The overall population was supported, at least in part, by memory T cells primed early in infection, as well as by recruitment of naive T cells at late times. Thus, these data show that memory inflation is maintained by a continuous replacement of short-lived, functional cells during chronic MCMV infection

Maternal vitamin D status in pregnancy and molar incisor hypomineralisation and hypomineralised second primary molars in the offspring at 7–9 years of age:a longitudinal study

Purpose: The study aimed to investigate associations between maternal vitamin D status during pregnancy and molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) among children. Methods: The study had a longitudinal design using prospectively collected data from 176 mother and child pairs. Mothers were initially recruited in a randomised controlled trial to assess a pregnancy exercise programme. Along with the 7-year follow-up, we invited the children to a dental examination. The exposure variable was maternal serum 25-hydroxyvitamin D in gestational weeks 18–22 and 32–36, categorised as insufficient (< 50 nmol/l) and sufficient (≥ 50 nmol/l). Negative binomial hurdle models were used to analyse potential associations between the exposure variables and MIH or HSPM. The models were adjusted for potential confounders. Results: Among the children (7–9 years old), 32% and 22% had at least one tooth with MIH or HSPM, respectively. A significant association was found between insufficient maternal vitamin D measured in gestational weeks 18–22 and the number of affected teeth among those with MIH at 7–9 years (adjusted RR = 1.82, 95% CI 1.13–2.93). Conclusion: Considering any limitations of the present study, it has been shown that insufficient maternal serum vitamin D at mid-pregnancy was associated with a higher number of affected teeth among the offspring with MIH at 7–9 years of age. Further prospective studies are needed to investigate whether this finding is replicable and to clarify the role of maternal vitamin D status during pregnancy and MIH, as well as HSPM, in children

Three mechanisms of hydrogen-induced dislocation pinning in tungsten

The high-flux deuterium plasma impinging on a divertor degrades the long-termthermo-mechanical performance of its tungsten plasma-facing components. A prime actor inthis is hydrogen embrittlement, a degradation phenomenon that involves the interactions between hydrogen and dislocations, the primary carriers of plasticity. Measuring such nanoscaleinteractions is still very challenging, which limits our understanding. Here, we demonstrate anexperimental approach that combines thermal desorption spectroscopy (TDS) andnanoindentation, allowing to investigate the effect of hydrogen on the dislocation mobility in tungsten. Dislocation mobility was found to be reduced after deuterium injection, which ismanifested as a ‘pop-in’ in the indentation stress-strain curve, with an average activation stressfor dislocation mobility that was more than doubled. All experimental results can be confidentlyexplained, in conjunction with experimental and numerical literature findings, by the simultaneous activation of three mechanisms responsible for dislocation pinning: (i) hydrogentrapping at pre-existing dislocations, (ii) hydrogen-induced vacancies, and (iii) stabilization ofvacancies by hydrogen, contributing respectively 38%, 52%, and 34% to the extra activationstress. These mechanisms are considered to be essential for the proper understanding and modeling of hydrogen embrittlement in tungsten

LiMeS-Lab:An Integrated Laboratory for the Development of Liquid–Metal Shield Technologies for Fusion Reactors

The liquid metal shield laboratory (LiMeS-Lab) will provide the infrastructure to develop, test, and compare liquid metal divertor designs for future fusion reactors. The main research topics of LiMeS-lab will be liquid metal interactions with the substrate material of the divertor, the continuous circulation and capillary refilling of the liquid metal during intense plasma heat loading and the retention of plasma particles in the liquid metal. To facilitate the research, four new devices are in development at the Dutch Institute for Fundamental Energy Research and the Eindhoven University of Technology: LiMeS-AM: a custom metal 3D printer based on powder bed fusion; LiMeS-Wetting, a plasma device to study the wetting of liquid metals on various substrates with different surface treatments; LiMeS-PSI, a linear plasma generator specifically adapted to operate continuous liquid metal loops. Special diagnostic protection will also be implemented to perform measurements in long duration shots without being affected by the liquid metal vapor; LiMeS-TDS, a thermal desorption spectroscopy system to characterize deuterium retention in a metal vapor environment. Each of these devices has specific challenges due to the presence and deposition of metal vapors that need to be addressed in order to function. In this paper, an overview of LiMeS-Lab will be given and the conceptual designs of the last three devices will be presented.</p

Referral patterns of children with poor growth in primary health care

Background. To promote early diagnosis and treatment of short stature, consensus meetings were held in the mid nineteen nineties in the Netherlands and the UK. This resulted in guidelines for referral. In this study we evaluate the referral pattern of short stature in primary health care using these guidelines, comparing it with cut-off values mentioned by the WHO. Methods. Three sets of referral rules were tested on the

How do you say ‘hello’? Personality impressions from brief novel voices

On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices

What Qualities Are Most Important to Making a Point of Care Test Desirable for Clinicians and Others Offering Sexually Transmitted Infection Testing?

To investigate the possible effects of different levels of attributes of a point-of-care test (POCT) on sexually transmitted infection (STI) professionals' decisions regarding an ideal POCT for STI(s).An online survey was designed based on a large-scale in-depth focus discussion study among STI experts and professionals. The last section of the survey "build your own POCT" was designed by employing the discrete choice experiment approach. Practicing clinicians from two venues, STI-related international conference attendees and U.S. STD clinic clinicians were invited to participate in the survey. Conditional logistical regression modeling was used for data analysis.Overall, 256 subjects took the online survey with 218 (85%) completing it. Most of the participants were STD clinic clinicians who already used some POCTs in their practice. "The time frame required" was identified as a major barrier that currently made it difficult to use STI POCTs. Chlamydia trachomatis was the organism chosen as the top priority for a new POCT, followed by a test that would diagnose early seroconversion for HIV, and a syphilis POCT. Without regard to organism type selected, sensitivity of 90-99% was always the most important attribute to be considered, followed by a cost of $20. However, when the test platform was prioritized for early HIV seroconversion or syphilis, sensitivity was still ranked as most important, but specificity was rated second most important.STI professionals preferred C. trachomatis as the top priority for a new POCT with sensitivity over 90%, low cost, and a very short completion time