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Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17-18) in the paracetamol group and 18 (16-18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67-76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Australian New Zealand Clinical Trials Registry ACTRN12609000444280.

β-lactam antibiotics are the most commonly used antibiotics for the empiric and targeted treatment of infection in the critically ill. Timely administration of an effective dose of β-lactams is critical to reduce infection-associated morbidity and mortality. Continuous infusion (CI) of β-lactam antibiotics is now an evidence-based strategy to optimise treatment in critically ill patients with infection. However, the widespread implementation of CI of β-lactams requires consideration of various practical and pharmaceutical related factors. The following addresses barriers to the implementation of CI of β-lactam antibiotics, including specific considerations for low resource settings, and aims to provide practical solutions for the translation of evidence into practice. •Continuous infusion (CI) of β-lactams reduces mortality in critically ill patients with infection.•Practical and pharmaceutic hurdles need to be addressed to ensure CI is effective beyond clinical trials.•Implementation barriers to CI of β-lactams are likely to differ between poor- and well-resourced settings.•An evidence-based response is needed for the global implementation of CI of β-lactams.

Background Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. Methods A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Results Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17-18) in the paracetamol group and 18 (16-18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67-76] per patient). The mean plus or minus standard deviation temperature was 37.4 plus or minus 0.5 degree C in the paracetamol group and 37.7 plus or minus 0.4 degree C in the saline group (absolute difference -0.3 degree C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. Conclusion The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000444280

Understanding the evolution of influenza A viruses in humans is important for surveillance and vaccine strain selection. We performed a phylogenetic analysis of 156 complete genomes of human H3N2 influenza A viruses collected between 1999 and 2004 from New York State, United States, and observed multiple co-circulating clades with different population frequencies. Strikingly, phylogenies inferred for individual gene segments revealed that multiple reassortment events had occurred among these clades, such that one clade of H3N2 viruses present at least since 2000 had provided the hemagglutinin gene for all those H3N2 viruses sampled after the 2002-2003 influenza season. This reassortment event was the likely progenitor of the antigenically variant influenza strains that caused the A/Fujian/411/2002-like epidemic of the 2003-2004 influenza season. However, despite sharing the same hemagglutinin, these phylogenetically distinct lineages of viruses continue to co-circulate in the same population. These data, derived from the first large-scale analysis of H3N2 viruses, convincingly demonstrate that multiple lineages can co-circulate, persist, and reassort in epidemiologically significant ways, and underscore the importance of genomic analyses for future influenza surveillance.

Understanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis.

Today's world poses a triple threat to the American population: infectious diseases, contamination of food and water, and bioattacks (biowarfare or bioterrorism). At least 17 countries are producing weapons of mass destruction using viruses, bacteria, or their toxins. AIDS, E. coli contamination, drug-resistant tuberculosis, and virulent flu strains are perhaps the best known of a host of disease threats. What these dangers have in common is the amount of data required to achieve solutions; in some cases, as much as a petabit (1 followed by 15 zeros) of data is required to study large numbers of samples from widespread locations. Firepower in the Lab examines how the nation can combat this triple threat by improving our ability to detect, measure, and monitor harmful biological agents. It explores the potential of today's exciting new laboratory automation and computer technologies as well as the emerging tools of molecular biology-how we can generate and analyze more data quickly and reduce human hands-on involvement, which inevitably introduces errors. The book discusses how to improve and apply technologies such as robotics, laboratory automation, \"lab-on-a-chip,\" bioinformatics, and Internet control innovations. It reviews lessons learned from our experience with pandemic flu viruses. It also presents strategies for developing new high-throughput technologies, including how to address the lack of public funding for critical research undertakings.

Tigr flu survey Published on 5 October online, the in-print version of the survey of more than 200 influenza virus sequences by The Institute for Genomic Research appears this week. Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality 1 , 2 . The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 ‘Spanish’ flu, one of the most deadly outbreaks in recorded history, which killed 30–50 million people worldwide, the 1957 ‘Asian’ flu, and the 1968 ‘Hong Kong’ flu 3 . Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.

Understanding the evolution of influenza A viruses in humans is important for surveillance and vaccine strain selection. We performed a phylogenetic analysis of 156 complete genomes of human H3N2 influenza A viruses collected between 1999 and 2004 from New York State, United States, and observed multiple co-circulating clades with different population frequencies. Strikingly, phylogenies inferred for individual gene segments revealed that multiple reassortment events had occurred among these clades, such that one clade of H3N2 viruses present at least since 2000 had provided the hemagglutinin gene for all those H3N2 viruses sampled after the 2002-2003 influenza season. This reassortment event was the likely progenitor of the antigenically variant influenza strains that caused the A/Fujian/411/2002-like epidemic of the 2003-2004 influenza season. However, despite sharing the same hemagglutinin, these phylogenetically distinct lineages of viruses continue to co-circulate in the same population. These data, derived from the first large-scale analysis of H3N2 viruses, convincingly demonstrate that multiple lineages can co-circulate, persist, and reassort in epidemiologically significant ways, and underscore the importance of genomic analyses for future influenza surveillance.

Over the last several decades, hydrogen fuel cell vehicles (FCVs) have recently emerged as a zero tailpipe-emission alternative to the battery electric vehicle (EV). FCVs have some important differences from gasoline internal combustion engine vehicles, and they have only been on the road for a few years. There are key questions about consumer reaction and response to operations and refueling. This paper presents the results of a \"ride-and-drive\" clinic series (n=182) held in 2007 with a Mercedes-Benz A-Class \"F-Cell\" hydrogen FCV. The clinic evaluated participant reactions to driving and riding in a FCV, as well as witnessing a vehicle-refueling event. Roughly 95% of respondents finished the clinic with either a positive or very positive impression of the F-Cell. More than 80% left with a positive overall impression of hydrogen. The majority expressed a willingness to travel five to ten minutes to find a hydrogen station. Approximately 50% would consider a 225 to 300 mile (360 to 480 kilometers) FCV range acceptable. Fifty percent would pay no more than a $3,000 US premium over a similar gasoline vehicle. In addition, clinic results are compared with the authors' previous study employing 24 F-Cells, which tracked respondents over a seven-month period. This comparative analysis helps to better discern which short-term effects may be influenced by the \"novelty\" effect and which are likely to persist due to new information.