Pregnancy has a minimal impact on the acute transcriptional signature to vaccination.

Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety

Spectral Line-by-Line Pulse Shaping of an On-Chip Microresonator Frequency Comb

We report, for the first time to the best of our knowledge, spectral phase characterization and line-by-line pulse shaping of an optical frequency comb generated by nonlinear wave mixing in a microring resonator. Through programmable pulse shaping the comb is compressed into a train of near-transform-limited pulses of \approx 300 fs duration (intensity full width half maximum) at 595 GHz repetition rate. An additional, simple example of optical arbitrary waveform generation is presented. The ability to characterize and then stably compress the frequency comb provides new data on the stability of the spectral phase and suggests that random relative frequency shifts due to uncorrelated variations of frequency dependent phase are at or below the 100 microHertz level.Comment: 18 pages, 4 figure

Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.

The epidemiology of Mycobacterium tuberculosis (Mtb) and M. africanum (Maf) suggests differences in their virulence, but the host immune profile to better understand the pathogenesis of tuberculosis (TB) have not been studied. We compared the transcriptomic and metabolic profiles between Mtb- and Maf-infected TB cases to identify host biomarkers associated with lineages-specific pathogenesis and response to anti-TB chemotherapy. Venous blood samples from Mtb- and Maf-infected patients obtained before and after anti-TB treatment were analyzed for cell composition, gene expression and metabolic profiles. Prior to treatment, similar transcriptomic profiles were seen in Maf- and Mtb-infected patients. In contrast, post treatment, over 1600 genes related to immune responses and metabolic diseases were differentially expressed between the groups. Notably, the upstream regulator hepatocyte nuclear factor 4-alpha (HNF4α), which regulated 15% of these genes, was markedly enriched. Serum metabolic profiles were similar in both group pre-treatment, but the decline in pro-inflammatory metabolites post treatment were most pronounced in Mtb-infected patients. Together, the differences in both peripheral blood transcriptomic and serum metabolic profiles between Maf- and Mtb-infected patients observed over the treatment period, might be indicative of intrinsic host factors related to susceptibility to TB and/or differential efficacy of the standard anti-TB treatment on the two lineages

Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

Neutrino Mass, Sneutrino Dark Matter and Signals of Lepton Flavor Violation in the MRSSM

We study the phenomenology of mixed-sneutrino dark matter in the Minimal R-Symmetric Supersymmetric Standard Model (MRSSM). Mixed sneutrinos fit naturally within the MRSSM, as the smallness (or absence) of neutrino Yukawa couplings singles out sneutrino A-terms as the only ones not automatically forbidden by R-symmetry. We perform a study of randomly generated sneutrino mass matrices and find that (i) the measured value of $\Omega_{DM}$ is well within the range of typical values obtained for the relic abundance of the lightest sneutrino, (ii) with small lepton-number-violating mass terms $m_{nn}^{2} {\tilde n} {\tilde n}$ for the right-handed sneutrinos, random matrices satisfying the $\Omega_{DM}$ constraint have a decent probability of satisfying direct detection constraints, and much of the remaining parameter space will be probed by upcoming experiments, (iii) the $m_{nn}^{2} {\tilde n} {\tilde n}$ terms radiatively generate appropriately small Majorana neutrino masses, with neutrino oscillation data favoring a mostly sterile lightest sneutrino with a dominantly mu/tau-flavored active component, and (iv) a sneutrino LSP with a significant mu component can lead to striking signals of e-mu flavor violation in dilepton invariant-mass distributions at the LHC.Comment: Revised collider analysis in Sec. 5 after fixing error in particle spectrum, References adde

Quantifying anatomical shape variations in neurological disorders

We develop a multivariate analysis of brain anatomy to identify the relevant shape deformation patterns and quantify the shape changes that explain corresponding variations in clinical neuropsychological measures. We use kernel Partial Least Squares (PLS) and formulate a regression model in the tangent space of the manifold of diffeomorphisms characterized by deformation momenta. The scalar deformation momenta completely encode the diffeomorphic changes in anatomical shape. In this model, the clinical measures are the response variables, while the anatomical variability is treated as the independent variable. To better understand the “shape—clinical response” relationship, we also control for demographic confounders, such as age, gender, and years of education in our regression model. We evaluate the proposed methodology on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database using baseline structural MR imaging data and neuropsychological evaluation test scores. We demonstrate the ability of our model to quantify the anatomical deformations in units of clinical response. Our results also demonstrate that the proposed method is generic and generates reliable shape deformations both in terms of the extracted patterns and the amount of shape changes. We found that while the hippocampus and amygdala emerge as mainly responsible for changes in test scores for global measures of dementia and memory function, they are not a determinant factor for executive function. Another critical finding was the appearance of thalamus and putamen as most important regions that relate to executive function. These resulting anatomical regions were consistent with very high confidence irrespective of the size of the population used in the study. This data-driven global analysis of brain anatomy was able to reach similar conclusions as other studies in Alzheimer’s Disease based on predefined ROIs, together with the identification of other new patterns of deformation. The proposed methodology thus holds promise for discovering new patterns of shape changes in the human brain that could add to our understanding of disease progression in neurological disorders

The limited importance of size-asymmetric light competition and growth of pioneer species in early secondary forest succession in Vietnam

It is generally believed that asymmetric competition for light plays a predominant role in determining the course of succession by increasing size inequalities between plants. Size-related growth is the product of size-related light capture and light-use efficiency (LUE). We have used a canopy model to calculate light capture and photosynthetic rates of pioneer species in sequential vegetation stages of a young secondary forest stand. Growth of the same saplings was followed in time as succession proceeded. Photosynthetic rate per unit plant mass (Pmass: mol C g−1 day−1), a proxy for plant growth, was calculated as the product of light capture efficiency [Φmass: mol photosynthetic photon flux density (PPFD) g−1 day−1] and LUE (mol C mol PPFD−1). Species showed different morphologies and photosynthetic characteristics, but their light-capturing and light-use efficiencies, and thus Pmass, did not differ much. This was also observed in the field: plant growth was not size-asymmetric. The size hierarchy that was present from the very early beginning of succession remained for at least the first 5 years. We conclude, therefore, that in slow-growing regenerating vegetation stands, the importance of asymmetric competition for light and growth can be much less than is often assumed

Organization-wide adoption of computerized provider order entry systems: a study based on diffusion of innovations theory

Background: Computerized provider order entry (CPOE) systems have been introduced to reduce medication errors, increase safety, improve work-flow efficiency, and increase medical service quality at the moment of prescription. Making the impact of CPOE systems more observable may facilitate their adoption by users. We set out to examine factors associated with the adoption of a CPOE system for inter-organizational and intra-organizational care. Methods: The diffusion of innovation theory was used to understand physicians and nurses attitudes and thoughts about implementation and use of the CPOE system. Two online survey questionnaires were distributed to all physicians and nurses using a CPOE system in county-wide healthcare organizations. The number of complete questionnaires analyzed was 134 from 200 nurses (67.0%) and 176 from 741 physicians (23.8%). Data were analyzed using descriptive-analytical statistical methods. Results: More nurses (56.7%) than physicians (31.3%) stated that the CPOE system introduction had worked well in their clinical setting (P andlt; 0.001). Similarly, more physicians (73.9%) than nurses (50.7%) reported that they found the system not adapted to their specific professional practice (P = andlt; 0.001). Also more physicians (25.0%) than nurses (13.4%) stated that they did want to return to the previous system (P = 0.041). We found that in particular the received relative advantages of the CPOE system were estimated to be significantly (P andlt; 0.001) higher among nurses (39.6%) than physicians (16.5%). However, physicians agreements with the compatibility of the CPOE and with its complexity were significantly higher than the nurses (P andlt; 0.001). Conclusions: Qualifications for CPOE adoption as defined by three attributes of diffusion of innovation theory were not satisfied in the study setting. CPOE systems are introduced as a response to the present limitations in paper-based systems. In consequence, user expectations are often high on their relative advantages as well as on a low level of complexity. Building CPOE systems therefore requires designs that can provide rather important additional advantages, e. g. by preventing prescription errors and ultimately improving patient safety and safety of clinical work. The decision-making process leading to the implementation and use of CPOE systems in healthcare therefore has to be improved. As any change in health service settings usually faces resistance, we emphasize that CPOE system designers and healthcare decision-makers should continually collect users feedback about the systems, while not forgetting that it also is necessary to inform the users about the potential benefits involved.Original Publication:Bahlol Rahimi, Toomas Timpka, Vivian Vimarlund, Srinivas Uppugunduri and Mikael Svensson, Organization-wide adoption of computerized provider order entry systems: a study based on diffusion of innovations theory, 2009, BMC MEDICAL INFORMATICS AND DECISION MAKING, (9), 52, .http://dx.doi.org/10.1186/1472-6947-9-52Licensee: BioMed Centralhttp://www.biomedcentral.com/. On the day of the defence date the original title of this article was "Adoption of computerized provider order entry systems: An organization-wide study based on diffusion of innovations theory"