Comparing Immunogenicity And Relative Effectiveness Of Siil-Pv (pneumosil) To Incumbent Streptococcus Pneumoniae Vaccines And Higher-Valent Vaccines In Development

Background. Streptococcus pneumoniae is an important cause of severe bacterial infections among children worldwide, and is the most common pathogenic cause of community-acquired pneumonia globally.1 There are currently multiple licensed pneumococcal conjugate vaccines that reduce both the risk of nasopharyngeal colonization (NP) and risk of developing IPD, in part by prompting an increase in serum antipolysaccharide immunoglobulin G (IgG) concentration.2 SIIL-PV (Pneumosil) is a vaccine developed by Serum Institute of India and PATH to protect against Streptococcus pneumoniae serotypes most common in LMICs, and at a lower comparative cost to its competitors.3 As this vaccine is relatively new, it is critical to understand the protection it offers compared to other pneumococcal vaccines (both licensed and in development) when administered to healthy infants. Methods. A literature review was conducted to identify head-to-head vaccine trials with published immunogenicity data, and data were subsequently used to calculate the geometric mean ratio and inverse variance weighted averages for each vaccine comparison. Finally, the relative risk of colonization after vaccination was estimated using the natural logarithm of the geometric mean ratio, and a serotype and ethnicity-specific b1ij coefficient (representing likelihood of NP acquisition), which was identified by fitting models to NP acquisition and immunogenicity data from a large pneumococcal vaccine trial of PCV7 and PCV13, which examined vaccine effects in different ethnic populations (Bedouin & Jewish). Results. Overall, 1164 publications were identified that contained the selected search terms, and 11 head-to-head vaccine trials selected that met the study criteria. Analyses of study data indicate Pneumosil offers similar protection against colonization when compared to PCV13 and Synflorix, for most serotypes on both 2+1 and 3+1 schedules. At the same time, PCV13 and PCV15 offer similar protection against colonization post-primary series on both vaccine schedules, and better overall protection against colonization after the booster dose. Finally, relative to PCV20, PCV13 was found to offer better vaccine protection against colonization after the booster dose on both schedules, with fewer comparative benefits post-primary series. Conclusion. Because Pneumosil offers comparable protection against pneumococcal colonization to incumbent vaccines such as Synflorix and PCV13, I predict Pneumosil would offer similar benefits to those which were observed when comparing PCV13 to PCV15 (with PCV13 providing comparable protection against colonization post-primary series on both schedules, and better protection after the booster dose), and PCV13 to PCV20 (where PCV13 offered better protection against colonization after the booster dose on both schedules, with fewer comparative benefits post-primary series)

Understanding effects of floral products on bee parasites: mechanisms, synergism, and ecological complexity

Floral nectar and pollen commonly contain diverse secondary metabolites. While these compounds are classically thought to play a role in plant defense, recent research indicates that they may also reduce disease in pollinators. Given that parasites have been implicated in ongoing bee declines, this discovery has spurred interest in the potential for ‘medicinal’ floral products to aid in pollinator conservation efforts. We review the evidence for antiparasitic effects of floral products on bee diseases, emphasizing the importance of investigating the mechanism underlying antiparasitic effects, including direct or host-mediated effects. We discuss the high specificity of antiparasitic effects of even very similar compounds, and highlight the need to consider how nonadditive effects of multiple compounds, and the post-ingestion transformation of metabolites, mediate the disease-reducing capacity of floral products. While the bulk of research on ntiparasitic effects of floral products on bee parasites has been conducted in the lab, we review evidence for the impact of such effects in the field, and highlight areas for future research at the floral product-bee disease interface. Such research has great potential both to enhance our understanding of the role of parasites in shaping plant-bee interactions, and the role of plants in determining bee-parasite dynamics. This understanding may in turn reveal new avenues for pollinator conservation

Non-perturbative dynamics of hot non-Abelian gauge fields: beyond leading log approximation

Many aspects of high-temperature gauge theories, such as the electroweak baryon number violation rate, color conductivity, and the hard gluon damping rate, have previously been understood only at leading logarithmic order (that is, neglecting effects suppressed only by an inverse logarithm of the gauge coupling). We discuss how to systematically go beyond leading logarithmic order in the analysis of physical quantities. Specifically, we extend to next-to-leading-log order (NLLO) the simple leading-log effective theory due to Bodeker that describes non-perturbative color physics in hot non-Abelian plasmas. A suitable scaling analysis is used to show that no new operators enter the effective theory at next-to-leading-log order. However, a NLLO calculation of the color conductivity is required, and we report the resulting value. Our NLLO result for the color conductivity can be trivially combined with previous numerical work by G. Moore to yield a NLLO result for the hot electroweak baryon number violation rate.Comment: 20 pages, 1 figur

Incorporating qualitative research methods into the monitoring and evaluation of neglected tropical disease programmes: a scoping literature review

This publication addresses the limited use of qualitative methods in neglected tropical disease (NTD) programmes. It describes a scoping literature review conducted to inform the development of a guide to inform the use of rapid qualitative assessments to strengthen NTD mass drug administration (MDA) programmes. The review assessed how qualitative methods are currently used by NTD programmes and identified qualitative approaches from other health and development programmes with the potential to strengthen the design of MDA interventions. Systematic review articles were reviewed and searched using key terms conducted on Google Scholar and PubMed. Results show that methods used by NTD programmes rely heavily on focus group discussions and in-depth interviews, often with time-consuming analysis and limited information on how results are applied. Results from other fields offered insight into a wider range of methods, including participatory approaches, and on how to increase programmatic uptake of findings. Recommendations on how to apply these findings to NTD control are made. The topic of human resources for qualitative investigations is explored and a guide to improve MDAs using qualitative methods is introduced. This guide has direct applicability across the spectrum of NTDs as well as other public health programmes

Organic electrode coatings for next-generation neural interfaces

Traditional neuronal interfaces utilize metallic electrodes which in recent years have reached a plateau in terms of the ability to provide safe stimulation at high resolution or rather with high densities of microelectrodes with improved spatial selectivity. To achieve higher resolution it has become clear that reducing the size of electrodes is required to enable higher electrode counts from the implant device. The limitations of interfacing electrodes including low charge injection limits, mechanical mismatch and foreign body response can be addressed through the use of organic electrode coatings which typically provide a softer, more roughened surface to enable both improved charge transfer and lower mechanical mismatch with neural tissue. Coating electrodes with conductive polymers or carbon nanotubes offers a substantial increase in charge transfer area compared to conventional platinum electrodes. These organic conductors provide safe electrical stimulation of tissue while avoiding undesirable chemical reactions and cell damage. However, the mechanical properties of conductive polymers are not ideal, as they are quite brittle. Hydrogel polymers present a versatile coating option for electrodes as they can be chemically modified to provide a soft and conductive scaffold. However, the in vivo chronic inflammatory response of these conductive hydrogels remains unknown. A more recent approach proposes tissue engineering the electrode interface through the use of encapsulated neurons within hydrogel coatings. This approach may provide a method for activating tissue at the cellular scale, however, several technological challenges must be addressed to demonstrate feasibility of this innovative idea. The review focuses on the various organic coatings which have been investigated to improve neural interface electrodes

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Computer software for business and specific purposes in wood industry

V 211 slovenskih mikro in majhnih lesnih podjetjih, katerih osnovna dejavnost (po SKD) zajema proizvodnjo pohištva za poslovne prostore, proizvodnjo kuhinjskega pohištva in proizvodnjo drugega pohištva, smo preučili razširjenost ter uporabo poslovnih in namenskih računalniških programov. Raziskava je temeljila na primerjalni analizi in oceni stanja programske opreme. Oceno stanja smo izvedli s pomočjo ankete, ki smo jo distribuirali prek različnih medijev. Odziv na anketo je bil v povprečju 23,7 %. Ocenimo lahko, da so računalniški programi v mikro in majhnih lesnih podjetjih na nekaterih področjih intenzivneje uporabljani kot na drugih. Ugotovili smo, da podjetja v večini uporabljajo pri poslovanju pisarniške programe, predvsem tiste podjetja Microsoft. Uporaba specializirane programske opreme je še precej omejena, saj jo pri poslovanju uporablja le 40 % preučevanih podjetij. Nekoliko bolj uporabljajo programsko opremo namenjeno konstruiranju (60 %).The range and usage of computer software for business and specific purposes were researched in 211 micro and minor wood firms, encompasing the production of office furniture, kitchen furniture and some other furniture as the basic activity, according to Statistical Classification Activities (SCA). The research was based on comparative analysis and software condition evaluation. Evaluation of the current situation was carried out by means of a questionnaire, distributed with the help of media. The response was as high as 23.7 %. It can be estimated that the computer software in these micro and minor wood firms is used more often in some areas than in others. It was found out that the firms use mainly office software- especially Microsoft ones. The usage of specialized software equipment is still quite limited in these firms. Only 40 % of the tested firms use is software for their business, meanwhile the equipment designed for construction is more frequently used (60 %)

The Genome Sequence of Caenorhabditis briggsae: A Platform for Comparative Genomics

The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes

Evidence for Shared Cognitive Processing of Pitch in Music and Language

Language and music epitomize the complex representational and computational capacities of the human mind. Strikingly similar in their structural and expressive features, a longstanding question is whether the perceptual and cognitive mechanisms underlying these abilities are shared or distinct – either from each other or from other mental processes. One prominent feature shared between language and music is signal encoding using pitch, conveying pragmatics and semantics in language and melody in music. We investigated how pitch processing is shared between language and music by measuring consistency in individual differences in pitch perception across language, music, and three control conditions intended to assess basic sensory and domain-general cognitive processes. Individuals’ pitch perception abilities in language and music were most strongly related, even after accounting for performance in all control conditions. These results provide behavioral evidence, based on patterns of individual differences, that is consistent with the hypothesis that cognitive mechanisms for pitch processing may be shared between language and music.National Science Foundation (U.S.). Graduate Research Fellowship ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant 5K99HD057522

Enhanced Functional Recovery in MRL/MpJ Mice after Spinal Cord Dorsal Hemisection

Adult MRL/MpJ mice have been shown to possess unique regeneration capabilities. They are able to heal an ear-punched hole or an injured heart with normal tissue architecture and without scar formation. Here we present functional and histological evidence for enhanced recovery following spinal cord injury (SCI) in MRL/MpJ mice. A control group (C57BL/6 mice) and MRL/MpJ mice underwent a dorsal hemisection at T9 (thoracic vertebra 9). Our data show that MRL/MpJ mice recovered motor function significantly faster and more completely. We observed enhanced regeneration of the corticospinal tract (CST). Furthermore, we observed a reduced astrocytic response and fewer micro-cavities at the injury site, which appear to create a more growth-permissive environment for the injured axons. Our data suggest that the reduced astrocytic response is in part due to a lower lesion-induced increase of cell proliferation post-SCI, and a reduced astrocytic differentiation of the proliferating cells. Interestingly, we also found an increased number of proliferating microglia, which could be involved in the MRL/MpJ spinal cord repair mechanisms. Finally, to evaluate the molecular basis of faster spinal cord repair, we examined the difference in gene expression changes in MRL/MpJ and C57BL/6 mice after SCI. Our microarray data support our histological findings and reveal a transcriptional profile associated with a more efficient spinal cord repair in MRL/MpJ mice