Setting, Mechanical, Morphological, Degradation and Antibacterial Properties of Brushite cements

Aims: This study aim was to develop high strength, antibacterial-releasing brushite cements with controllable setting and porosity for bone-filling. Materials and Methods: Monocalcium phosphate monohydrate (MCPM) was reacted with equimolar β-tricalcium phosphate (TCP) and 800mM aqueous citric acid (CA) containing 0, 20, or 40wt% of antibacterial ε-polylysine (PLS). The large MCPM monoclinic crystals (10x100x500 micron) were used as received or after grinding. The powder to liquid ratio was 3:1 or 4:1. Setting kinetics, mechanical strengths, fracture surface morphologies, degradation rates, and PLS release was undertaken. Additionally, MRSA colony forming units (CFU) on set material discs with 0 versus 40wt% PLS and in surrounding broth medium was compared. Results Use of smaller particles and increased PLS lead to formation of more stable intermediate complexes and slower Brushite formation. Formulations with intermediate MCPM particle size and higher powder content had significantly higher flexural strengths. Pores / channels with dimensions comparable with those of the original MCPM crystals were detected on the fracture surfaces. Dissolution rates were affected by MCPM particle size but not PLS content. PLS release occurred primarily in the first 24 hours of set disc immersion in water. Addition of PLS enabled MRSA growth to decline from 1.8 x 107 to 2.5 x 104 on a set disc and from 2.0 x 109 to 1.2 x 104 CFU in the surrounding medium. . Conclusion and significance The above antibacterial Brushite cements could be employed in the treatment of infected bone (e.g. periodontitis, implantitis, osteomyelitis). Controlled setting is required to minimise leakage away from the required site of application. The channels in the cements and dissolution will allow bone cell penetration and provide ions for new bone formation respectively. The higher strengths will enable application in greater load bearing clinical situations

What Drives Wind and Solar Energy Investment in India and China?

This research is motivated by the need to transform the basis of energy systems from fossil fuels to renewable sources. As well as the imperative of climate change, this transformation is needed to create development trajectories for economies that are genuinely sustainable over the long term. Our objectives are therefore both environmental and developmental. Understanding what drove low-carbon investments in the past is the key to identifying the drivers of investment in the future. In this regard, low-carbon investment decisions are not technical questions of optimal asset allocation. Rather, understanding these decisions requires an approach rooted in political economy, which assesses the motivations and incentives of the different actors involved, and how these interact. Understanding the dynamics of this process is the first step in shaping it. This research concentrates on private investment. Of the US$45 trillion of investments that the International Energy Agency (IEA) estimates are required by 2050 to reduce global carbon emissions by half, it is assumed that 85 per cent will need to come from the private sector. Annually, this averages at a little over US$1 trillion, half of which will fund the replacement of existing technologies, largely in developed countries. The remaining US$530bn is investment in new capacity, the bulk of which (US$400bn pa) will be in developing countries (IEA 2008). Our focus is on the determinants of low-carbon investment in the world’s two largest emerging economies: China and India. While these countries are responsible for the biggest growth in carbon emissions, China is now the largest global investor in renewable energy and India saw the highest growth rate in recent times between 2010 and 2011 (BNEF 2012).UK Department for International Developmen

Normalization factors for magnetic relaxation of small particle systems in non-zero magnetic field

We critically discuss relaxation experiments in magnetic systems that can be characterized in terms of an energy barrier distribution, showing that proper normalization of the relaxation data is needed whenever curves corresponding to different temperatures are to be compared. We show how these normalization factors can be obtained from experimental data by using the $T \ln(t/\tau_0)$ scaling method without making any assumptions about the nature of the energy barrier distribution. The validity of the procedure is tested using a ferrofluid of Fe_3O_4 particles.Comment: 5 pages, 6 eps figures added in April 22, to be published in Phys. Rev. B 55 (1 April 1997

Late Miocene to early Pliocene biofacies of Wanganui and Taranaki Basins, New Zealand: Applications to paleoenvironmental and sequence stratigraphic analysis

The Matemateaonga Formation is late Miocene to early Pliocene (upper Tongaporutuan to lower Opoitian New Zealand Stages) in age. The formation comprises chiefly shellbeds, siliciclastic sandstone, and siltstone units and to a lesser extent non-marine and shallow marine conglomerate and rare paralic facies. The Matemateaonga Formation accumulated chiefly in shelf paleoenvironments during basement onlap and progradation of a late Miocene to early Pliocene continental margin wedge in the Wanganui and Taranaki Basins. The formation is strongly cyclothemic, being characterised by recurrent vertically stacked facies successions, bounded by sequence boundaries. These facies accumulated in a range of shoreface to mid-outer shelf paleoenvironments during conditions of successively oscillating sea level. This sequential repetition of facies and the biofacies they enclose are the result of sixth-order glacio-eustatic cyclicity. Macrofaunal associations have been identified from statistical analysis of macrofossil occurrences collected from multiple sequences. Each association is restricted to particular lithofacies and stratal positions and shows a consistent order and/or position within the sequences. This pattern of temporal paleoecologic change appears to be the result of lateral, facies-related shifting of broad biofacies belts, or habitat-tracking, in response to fluctuations of relative sea level, sediment flux, and other associated paleoenvironmental variables. The associations also show strong similarity in terms of their generic composition to biofacies identified in younger sedimentary strata and the modern marine benthic environment in New Zealand

Time and dose dependency of bone-sarcomas in patients injected with radium-224

The time course and dose dependency of the incidence of bone-sarcomas among 900 German patients treated with high doses of radium-224 is analysed in terms of a proportional hazards model with a log-normal dependency of time to tumor and a linear-quadratic dose relation. The deduced dose dependency agrees well with a previous analysis in terms of a non-parametric proportional hazards model, and confirms the temporal distribution which has been used in the Radioepidemiological Tables of NIH. However, the linear-quadratic dose-response model gives a risk estimate for low doses which is somewhat less than half that obtained under the assumption of linearity. Dedicated to Prof. W. Jacobi on the occasion of his 60th birthday Work performed under Euratom contracts BI6-D-083-D, BI6-F-111-D, U.S. Department of Energy contract DE-AC 02-76 EV-00119, the U.S. National Cancer Institut

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Comparison of Characteristics and Complications in Men Versus Women Undergoing Chronic Total Occlusion Percutaneous Intervention

Gender differences exist in clinical outcomes after routine percutaneous coronary intervention (PCI), but studies reporting such outcomes after chronic total occlusion (CTO) PCI are limited. We assessed the characteristics and outcomes of female patients undergoing CTO PCI. We retrospectively analyzed a dedicated national (United Kingdom) prospective CTO database from 2011 to 2015 for outcomes and characteristics of female patients undergoing CTO PCI (unmatched and propensity matched). Female patients constituted 20.5% (n = 260 of 1,271) of the unmatched cohort and 33.3% (n = 233 of 699) of the matched cohort and were more likely to be older (women aged >70 years, 48% in the unmatched and 45% in the matched cohort). An increased inhospital complication rate was observed in female patients (unmatched: 10% women vs 4.45% men, p = 0.0012, and matched 9.87% women vs 3.86% men, p = 0.0032). Coronary perforation, bleeding, and contrast-induced nephropathy were more frequently observed in female patients. Femoral access site with >6 French sheath was associated with an increased risk of bleeding. Presence of calcification in the CTO artery was associated with coronary perforation (grade III) in female patients in the matched cohort (p = 0.007). Female patients undergoing CTO PCI were older and experienced increased of inhospital complications. Increased awareness of these complications could influence the selection of access site and sheath size, the need for prehydration, judicious choice of balloon size, collateral selection, and wire placement in female patients undergoing CTO PCI

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics

Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces

Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health-associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body. IMPORTANCE Many health care professionals use antibiotic prophylaxis strategies to prevent infection after surgery. This practice is under debate since it enhances the spread of antibiotic resistance. Another important reason to avoid nonessential use of antibiotics, the impact on our microbiome, has hardly received attention. In this study, we assessed the impact of antibiotics on the human microbial ecology at two niches. We followed the oral and gut microbiomes in 66 individuals from before, immediately after, and up to 12 months after exposure to different antibiotic classes. The salivary microbiome recovered quickly and was surprisingly robust toward antibiotic-induced disturbance. The fecal microbiome was severely affected by most antibiotics: for months, health-associated butyrate-producing species became strongly underrepresented. Additionally, there was an enrichment of genes associated with antibiotic resistance. Clearly, even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome

A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant staphylococcus aureus pandemic

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drug-resistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens