Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis.

Bacillus anthracis is the causative agent of anthrax, a disease that affects wildlife, livestock, and humans. Protection against anthrax is primarily afforded by immunity to the B. anthracis protective antigen (PA), particularly PA domains 4 and 1. To further the development of an orally delivered human vaccine for mass vaccination against anthrax, we produced Salmonella enterica serovar Typhimurium expressing full-length PA, PA domains 1 and 4, or PA domain 4 using codon-optimized PA DNA fused to the S. enterica serovar Typhi ClyA and under the control of the ompC promoter. Oral immunization of A/J mice with Salmonella expressing full-length PA protected five of six mice against a challenge with 10(5) CFU of aerosolized B. anthracis STI spores, whereas Salmonella expressing PA domains 1 and 4 provided only 25% protection (two of eight mice), and Salmonella expressing PA domain 4 or a Salmonella-only control afforded no measurable protection. However, a purified recombinant fusion protein of domains 1 and 4 provided 100% protection, and purified recombinant 4 provided protection in three of eight immunized mice. Thus, we demonstrate for the first time the efficacy of an oral S. enterica-based vaccine against aerosolized B. anthracis spores

Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos

Background The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. Methodology/Principal Findings Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001). Conclusions H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM

Group Incentives and Rational Voting

Our model describes competition between groups driven by the choices of self-interested voters within groups. Within a Poisson voting environment, parties observe aggregate support from groups and can allocate prizes or punishments to them. In a tournament style analysis, the model characterizes how contingent allocation of prizes based on relative levels of support affects equilibrium voting behavior. In addition to standard notions of pivotality, voters influence the distribution of prizes across groups. Such prize pivotality supports positive voter turnout even in non-competitive electoral settings. The analysis shows that competition for a prize awarded to the most supportive group is only stable when two groups actively support a party. However, competition among groups to avoid punishment is stable in environments with any number of groups. We conclude by examining implications for endogenous group formation and how politicians structure the allocation of rewards and punishments.Comment: 34 pages, 1 figur

The Dental Neglect Scale in adolescents

<p>Abstract</p> <p>Background</p> <p>Dental neglect has been found to be related to poor oral health, a tendency not to have had routine check-ups, and a longer period of time since the last dental appointment in samples of children and adults. The Dental Neglect Scale (DNS) has been found to be a valid measure of dental neglect in samples of children and adults, and may be valid for adolescents as well. We administered the DNS to a sample of adolescents and report on the relationships between the DNS and oral health status, whether or not the adolescent has been to the dentist recently for routine check-ups, and whether or not the adolescent currently goes to a dentist. We also report the internal and test-retest reliabilities of the DNS in this sample, as well as the results of an exploratory factor analysis.</p> <p>Methods</p> <p>One hundred seventeen adolescents from seven youth groups in the Seattle-Tacoma metropolitan area (Washington State, U.S.) completed the DNS and indicated whether they currently go to a dentist, while parents indicated whether the adolescent had a check-up in the previous three years. Adolescents also received a dental screening. Sixty six adolescents completed the questionnaire twice. T-tests were used to compare DNS scores of adolescents who have visible caries or not, adolescents who have had a check-up in the past three years or not, and adolescents who currently go to a dentist or not. Internal reliability was measured by Cronbach's alpha, and test-rest reliability was measured by intra-class correlation. Factor analysis (Varimax rotation) was used to examine the factor structure.</p> <p>Results</p> <p>In each comparison, significantly higher DNS scores were observed in adolescents with visible caries, who have not had a check-up in the past three years, or who do not go to a dentist (all p values < 0.05). The test-retest reliability of the DNS was high (ICC = 0.81), and its internal reliability was acceptable (Cronbach's alpha = 0.60). Factor analysis yielded two factors, characterized by home care and visiting a dentist.</p> <p>Conclusion</p> <p>The DNS appears to operate similarly in this sample of adolescents as it has in other samples of children and adults.</p

Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies

Background: Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies. Methods and Findings: Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings. We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services. Conclusions: Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings

The results of arthroscopic anterior stabilisation of the shoulder using the bioknotless anchor system

<p>Abstract</p> <p>Background</p> <p>Shoulder instability is a common condition, particularly affecting a young, active population. Open capsulolabral repair is effective in the majority of cases, however arthroscopic techniques, particularly using suture anchors, are being used with increasing success.</p> <p>Methods</p> <p>15 patients with shoulder instability were operated on by a single surgeon (VK) using BioKnotless anchors (DePuy Mitek, Raynham, MA). The average length of follow-up was 21 months (17 to 31) with none lost to follow-up. Constant scores in both arms, patient satisfaction, activity levels and recurrence of instability was recorded.</p> <p>Results</p> <p>80% of patients were satisfied with their surgery. 1 patient suffered a further dislocation and another had recurrent symptomatic instability. The average constant score returned to 84% of that measured in the opposite (unaffected) shoulder. There were no specific post-operative complications encountered.</p> <p>Conclusion</p> <p>In terms of recurrence of symptoms, our results show success rates comparable to other methods of shoulder stabilisation. This technique is safe and surgeons familiar with shoulder arthroscopy will not encounter a steep learning curve. Shoulder function at approximately 2 years post repair was good or excellent in the majority of patients and it was observed that patient satisfaction was correlated more with return to usual activities than recurrence of symptoms.</p

Contrasting Transcriptional Responses of a Virulent and an Attenuated Strain of Mycobacterium tuberculosis Infecting Macrophages

Along with the recent identification of single nucleotide polymorphisms in H37Ra when compared to H37Rv, our demonstration of differential expression of PhoP-regulated and ESX-1 region-related genes during macrophage infection further highlights the significance of these genes in the attenuation of H37Ra

Quantum Measurement Theory in Gravitational-Wave Detectors

The fast progress in improving the sensitivity of the gravitational-wave (GW) detectors, we all have witnessed in the recent years, has propelled the scientific community to the point, when quantum behaviour of such immense measurement devices as kilometer-long interferometers starts to matter. The time, when their sensitivity will be mainly limited by the quantum noise of light is round the corner, and finding the ways to reduce it will become a necessity. Therefore, the primary goal we pursued in this review was to familiarize a broad spectrum of readers with the theory of quantum measurements in the very form it finds application in the area of gravitational-wave detection. We focus on how quantum noise arises in gravitational-wave interferometers and what limitations it imposes on the achievable sensitivity. We start from the very basic concepts and gradually advance to the general linear quantum measurement theory and its application to the calculation of quantum noise in the contemporary and planned interferometric detectors of gravitational radiation of the first and second generation. Special attention is paid to the concept of Standard Quantum Limit and the methods of its surmounting.Comment: 147 pages, 46 figures, 1 table. Published in Living Reviews in Relativit

Laboratory layered latte

Inducing thermal gradients in fluid systems with initial, well-defined density gradients results in the formation of distinct layered patterns, such as those observed in the ocean due to double-diffusive convection. In contrast, layered composite fluids are sometimes observed in confined systems of rather chaotic initial states, for example, lattes formed by pouring espresso into a glass of warm milk. Here, we report controlled experiments injecting a fluid into a miscible phase and show that, above a critical injection velocity, layering emerges over a time scale of minutes. We identify critical conditions to produce the layering, and relate the results quantitatively to double-diffusive convection. Based on this understanding, we show how to employ this single-step process to produce layered structures in soft materials, where the local elastic properties vary step-wise along the length of the material