Neutropenia as an adverse event following vaccination : results from randomized clinical trials in healthy adults and systematic review

Background : In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology : We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings : Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions : It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events

Phase sensitivity to axial strain of microstrustured optical silica fibers

International audienceWe compare, thanks to a Sagnac interferometer, the phase sensitivity to strain of different microstructured optical silica fibers (MSF) that we design and fabricate. Our results show that when a same elongation is applied to different MSF, the induced phase change is equal or lower than the one obtained for a standard fiber, showing no advantage on this parameter for sensing applications

Later cART Initiation in Migrant Men from Sub-Saharan Africa without Advanced HIV Disease in France

International audienceObjectiveTo compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care.MethodsAntiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002–2010, with CD4 cell counts >200/μL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200–349, 350-499, ≥500/μL), we examined the crude time until cART initiation within three years after enrolment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrolment period, region of care, plasma viral load, and HBV/HBC coinfection.ResultsAmong 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1–28) and 20% (95%CI, 2–38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM.ConclusionSSA/NFW migrant men living in France with CD4 >350/μL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible

Auditory-motor entrainment and phonological skills: precise auditory timing hypothesis (PATH)

Phonological skills are enhanced by music training, but the mechanisms enabling this cross-domain enhancement remain unknown. To explain this cross-domain transfer, we propose a precise auditory timing hypothesis (PATH) whereby entrainment practice is the core mechanism underlying enhanced phonological abilities in musicians. Both rhythmic synchronization and language skills such as consonant discrimination, detection of word and phrase boundaries, and conversational turn-taking rely on the perception of extremely fine-grained timing details in sound. Auditory-motor timing is an acoustic feature which meets all five of the pre-conditions necessary for cross-domain enhancement to occur (Patel, 2011, 2012, 2014). There is overlap between the neural networks that process timing in the context of both music and language. Entrainment to music demands more precise timing sensitivity than does language processing. Moreover, auditory-motor timing integration captures the emotion of the trainee, is repeatedly practiced, and demands focused attention. The PATH predicts that musical training emphasizing entrainment will be particularly effective in enhancing phonological skills

Incipient Social Groups: An Analysis via In-Vivo Behavioral Tracking

Social psychology is fundamentally the study of individuals in groups, yet there remain basic unanswered questions about group formation, structure, and change. We argue that the problem is methodological. Until recently, there was no way to track who was interacting with whom with anything approximating valid resolution and scale. In the current study we describe a new method that applies recent advances in image-based tracking to study incipient group formation and evolution with experimental precision and control. In this method, which we term "in vivo behavioral tracking," we track individuals' movements with a high definition video camera mounted atop a large field laboratory. We report results of an initial study that quantifies the composition, structure, and size of the incipient groups. We also apply in-vivo spatial tracking to study participants' tendency to cooperate as a function of their embeddedness in those crowds. We find that participants form groups of seven on average, are more likely to approach others of similar attractiveness and (to a lesser extent) gender, and that participants' gender and attractiveness are both associated with their proximity to the spatial center of groups (such that women and attractive individuals are more likely than men and unattractive individuals to end up in the center of their groups). Furthermore, participants' proximity to others early in the study predicted the effort they exerted in a subsequent cooperative task, suggesting that submergence in a crowd may predict social loafing. We conclude that in vivo behavioral tracking is a uniquely powerful new tool for answering longstanding, fundamental questions about group dynamics

Pediatric Responses to Fundamental and Formant Frequency Altered Auditory Feedback: A Scoping Review

Purpose: The ability to hear ourselves speak has been shown to play an important role in the development and maintenance of fluent and coherent speech. Despite this, little is known about the developing speech motor control system throughout childhood, in particular if and how vocal and articulatory control may differ throughout development. A scoping review was undertaken to identify and describe the full range of studies investigating responses to frequency altered auditory feedback in pediatric populations and their contributions to our understanding of the development of auditory feedback control and sensorimotor learning in childhood and adolescence. Method: Relevant studies were identified through a comprehensive search strategy of six academic databases for studies that included (a) real-time perturbation of frequency in auditory input, (b) an analysis of immediate effects on speech, and (c) participants aged 18 years or younger. Results: Twenty-three articles met inclusion criteria. Across studies, there was a wide variety of designs, outcomes and measures used. Manipulations included fundamental frequency (9 studies), formant frequency (12), frequency centroid of fricatives (1), and both fundamental and formant frequencies (1). Study designs included contrasts across childhood, between children and adults, and between typical, pediatric clinical and adult populations. Measures primarily explored acoustic properties of speech responses (latency, magnitude, and variability). Some studies additionally examined the association of these acoustic responses with clinical measures (e.g., stuttering severity and reading ability), and neural measures using electrophysiology and magnetic resonance imaging. Conclusion: Findings indicated that children above 4 years generally compensated in the opposite direction of the manipulation, however, in several cases not as effectively as adults. Overall, results varied greatly due to the broad range of manipulations and designs used, making generalization challenging. Differences found between age groups in the features of the compensatory vocal responses, latency of responses, vocal variability and perceptual abilities, suggest that maturational changes may be occurring in the speech motor control system, affecting the extent to which auditory feedback is used to modify internal sensorimotor representations. Varied findings suggest vocal control develops prior to articulatory control. Future studies with multiple outcome measures, manipulations, and more expansive age ranges are needed to elucidate findings

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

International audienceAdult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy

Systemic sclerosis : state of the art on clinical practice guidelines

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains 'Vascular & Ulcers' (ie, non-pharmacological approach to digital ulcer), 'PAH' (ie, screening and treatment), 'Treatment' and 'Juveniles' (ie, evaluation of juveniles with Raynaud's phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-) pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation

Evidence for multiple rhythmic skills

Rhythms, or patterns in time, play a vital role in both speech and music. Proficiency in a number of rhythm skills has been linked to language ability, suggesting that certain rhythmic processes in music and language rely on overlapping resources. However, a lack of understanding about how rhythm skills relate to each other has impeded progress in understanding how language relies on rhythm processing. In particular, it is unknown whether all rhythm skills are linked together, forming a single broad rhythmic competence, or whether there are multiple dissociable rhythm skills. We hypothesized that beat tapping and rhythm memory/sequencing form two separate clusters of rhythm skills. This hypothesis was tested with a battery of two beat tapping and two rhythm memory tests. Here we show that tapping to a metronome and the ability to adjust to a changing tempo while tapping to a metronome are related skills. The ability to remember rhythms and to drum along to repeating rhythmic sequences are also related. However, we found no relationship between beat tapping skills and rhythm memory skills. Thus, beat tapping and rhythm memory are dissociable rhythmic aptitudes. This discovery may inform future research disambiguating how distinct rhythm competencies track with specific language functions

Molecular Hydrogen in the Damped Ly alpha Absorber of Q1331+170

We used HST/STIS to obtain the spectrum of molecular hydrogen associated with the damped Ly$\alpha$ system at $z_{\rm abs}=1.7765$ toward the quasar Q1331+170 at $z_{\rm em}=2.084$. Strong ${\rm H}_2$ absorption was detected, with a total ${\rm H}_2$ column density of $N({\rm H}_2)=(4.45\pm 0.36)\times 10^{19} {\rm cm^{-2}}$.The molecular hydrogen fraction is $f_{{\rm H}_2}=\frac{2N_{\rm H_2}}{N_{\rm HI}+2N_{\rm H_2}}=(5.6\pm 0.7)$, which is the greatest value reported so far in any redshifted damped Ly$\alpha$ system. This results from the combined effect of a relatively high dust-to-gas ratio, a low gas temperature, and an extremely low ambient UV radiation field. Based on the observed population of $J$ states, we estimate the photo-absorption rate to be $R_{\rm abs}=(7.6\pm 2.4)\times 10^{-13} {\rm s^{-1}}$, corresponding to a local UV radiation field of $J(1000{\rm \AA})\approx 2.1\times 10^{-3} J_{1000{\rm \AA},\odot}$, where $J_{1000{\rm \AA},\odot}$ is the UV intensity at $1000 \AA$ in the solar neighborhood. This is comparable with the metagalactic UV background intensity at this redshift, and implies an extremely low star formation rate in the absorber's environment. The observed CO-to-H$_2$ column density ratio is $\frac{N_{\rm CO}}{N_{\rm H_2}}<2.5\times 10^{-7}$, which is similar to the value measured for diffuse molecular clouds in the Galactic ISM. Finally, applying the inferred physical conditions to the observed C I fine structure excitation (Songaila {\it et al.} 1994), we estimate the cosmic microwave background temperature to be $T_{\rm CMB}=(7.2\pm 0.8) {\rm K}$ at $z=1.77654$, consistent with the predicted value of $7.566 {\rm K}$ from the standard cosmology.Comment: Accepted for publication, Astrophysical Journal. Abstract abbreviate