Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Personalized Drug Dosage – Closing the Loop

A brief account is given of various approaches to the individualization of drug dosage, including the use of pharmacodynamic markers, therapeutic monitoring of plasma drug concentrations, genotyping, computer-guided dosage using ‘dashboards’, and automatic closed-loop control of pharmacological action. The potential for linking the real patient to his or her ‘virtual twin’ through the application of physiologically-based pharmacokinetic modeling is also discussed

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC

Authentic Literacy in the Classroom: America and Middle East Connections

Authentic Literacy in the classroom Authentic literacy in the classroom is becoming a more common practice amongst educators. Research has indicated that activities which center around real-world experiences can increase student motivation, literacy learning, and instill a purpose for learning rather than instruction which is centered around isolated activities with no real purpose or relevance to their real lives. Middle Eastern culture and relevant literature were used in this study as a focus on implications of authentic lessons to foster connections between American students and the Middle East, increase student motivation, and track changes in previously held biases. The results of this study suggest that authentic literacy can be used to support literacy processes, increase student motivation, and shift student thinking towards a more tolerant and open-minded view of societies in general. Authentic Literacy in the Classroom: America and Middle Eastern connections A common complaint or challenge that is faced with school teachers and authentic literacy is the lack of time allowed between the standardized tests and core curriculum, lack of support from administration (in order to permit students participation in authentic activities), and most commonly-teachers do not know how to implement it in the classroom and make it part of their daily instruction. According to Purcell-Gates, Duke, and Martinea

Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy

Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activatio

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Research into the Health Benefits of Sprint Interval Training Should Focus on Protocols with Fewer and Shorter Sprints

Over the past decade, it has been convincingly shown that regularly performing repeated brief supramaximal cycle sprints (sprint interval training [SIT]) is associated with aerobic adaptations and health benefits similar to or greater than with moderate-intensity continuous training (MICT). SIT is often promoted as a time-efficient exercise strategy, but the most commonly studied SIT protocol (4–6 repeated 30-s Wingate sprints with 4 min recovery, here referred to as ‘classic’ SIT) takes up to approximately 30 min per session. Combined with high associated perceived exertion, this makes classic SIT unsuitable as an alternative/adjunct to current exercise recommendations involving MICT. However, there are no indications that the design of the classic SIT protocol has been based on considerations regarding the lowest number or shortest duration of sprints to optimise time efficiency while retaining the associated health benefits. In recent years, studies have shown that novel SIT protocols with both fewer and shorter sprints are efficacious at improving important risk factors of noncommunicable diseases in sedentary individuals, and provide health benefits that are no worse than those associated with classic SIT. These shorter/easier protocols have the potential to remove many of the common barriers to exercise in the general population. Thus, based on the evidence summarised in this current opinion paper, we propose that there is a need for a fundamental change in focus in SIT research in order to move away from further characterising the classic SIT protocol and towards establishing acceptable and effective protocols that involve minimal sprint durations and repetitions

The impact of life tables adjusted for smoking on the socio-economic difference in net survival for laryngeal and lung cancer.

BACKGROUND: Net survival is a key measure in cancer control, but estimates for cancers that are strongly associated with smoking may be biased. General population life tables represent background mortality in net survival, but may not adequately reflect the higher mortality experienced by smokers. METHODS: Life tables adjusted for smoking were developed, and their impact on net survival and inequalities in net survival for laryngeal and lung cancers was examined. RESULTS: The 5-year net survival estimated with smoking-adjusted life tables was consistently higher than the survival estimated with unadjusted life tables: 7% higher for laryngeal cancer and 1.5% higher for lung cancer. The impact of using smoking-adjusted life tables was more pronounced in affluent patients; the deprivation gap in 5-year net survival for laryngeal cancer widened by 3%, from 11% to 14%. CONCLUSIONS: Using smoking-adjusted life tables to estimate net survival has only a small impact on the deprivation gap in survival, even when inequalities are substantial. Adjusting for the higher, smoking-related background mortality did increase the estimates of net survival for all deprivation groups, and may be more important when measuring the public health impact of differences or changes in survival, such as avoidable deaths or crude probabilities of death

The cytotoxic T cell proteome and its shaping by the kinase mTOR

High-resolution mass spectrometry maps the cytotoxic T lymphocyte (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes and mTORC1 selectively repressed and promoted expression of subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for mTORC1 negative control of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P(3)) production in CTL. mTORC1 was shown to repress PtdIns(3,4,5)P(3) production and to determine the mTORC2 requirement for activation of the kinase Akt. Unbiased proteomic analysis thus provides a comprehensive understanding of CTL identity and mTORC1 control of CTL function