Sepsis – An Impendence That Needs a Global Solution Know Safety – No Infection

Sepsis has been called a hidden public health disaster. Sepsis arises from the host response to infection, which is directed to kill the invading pathogens. It is an extreme response to an infection and one of the most common causes of multiorgan failure. The human body sends a flood of chemicals into the bloodstream to fight the threat. This causes widespread inflammation which, over time, can slow blood flow and damage the organs. Sepsis is clinically diagnosed by a combination of clinical signs, laboratory tests and microbiologically confirmed by the detection of bacteria in blood by culture. Early and aggressive management with appropriate antimicrobials and rapid and complete hemodynamic stabilization has been shown to be associated with improved outcomes. Detecting sepsis early and starting immediate treatment is often the difference between life and death

Making light work of heavy metal contamination::The potential for coupling bioremediation with bioenergy production

Intense anthropogenic activity continues to expose the natural environment to heavy metal contamination. Whilst a number of physical and chemical solutions for remediation exist, the use of higher plants and algae for clean‐up of contaminated landscapes, termed “phytoremediation” and “phycoremediation”, respectively, offer an attractive and sustainable alternative. However, these remediation processes will always lead to a high‐moisture, heavy metal‐contaminated biomass, which must be further processed to partition, or render inert, the metal contaminants. Conversion of this metal‐rich biomass into second‐generation biofuels offers a useful route to subsidise the economics of remediation activities. Here we briefly review the various methods for bioremediation of heavy metals, and discuss the potential to produce bioenergy from these biomass sources. Ultimately, coupling the bioremediation activity to bioenergy production gives far‐reaching social and economic benefits; however, established processes such as direct combustion and anaerobic digestion risk releasing heavy metals back into the environment. Alternatively, thermochemical conversions such as pyrolysis or hydrothermal liquefaction (HTL) offer significant advantages in terms of the segregation of metals into a relatively inert and compact solid phase while producing a biocrude oil for bioenergy production. In addition, preliminary work suggests that the HTL process can also be used to partition essential macronutrients, such as N, P and K, into an aqueous medium, allowing additional nutrient recycling

Lessons from dynamic cadaver and invasive bone pin studies: do we know how the foot really moves during gait?

Background: This paper provides a summary of a Keynote lecture delivered at the 2009 Australasian Podiatry Conference. The aim of the paper is to review recent research that has adopted dynamic cadaver and invasive kinematics research approaches to better understand foot and ankle kinematics during gait. It is not intended to systematically cover all literature related to foot and ankle kinematics (such as research using surface mounted markers). Since the paper is based on a keynote presentation its focuses on the authors own experiences and work in the main, drawing on the work of others where appropriate Methods: Two approaches to the problem of accessing and measuring the kinematics of individual anatomical structures in the foot have been taken, (i) static and dynamic cadaver models, and (ii) invasive in-vivo research. Cadaver models offer the advantage that there is complete access to all the tissues of the foot, but the cadaver must be manipulated and loaded in a manner which replicates how the foot would have performed when in-vivo. The key value of invasive in-vivo foot kinematics research is the validity of the description of foot kinematics, but the key difficulty is how generalisable this data is to the wider population. Results: Through these techniques a great deal has been learnt. We better understand the valuable contribution mid and forefoot joints make to foot biomechanics, and how the ankle and subtalar joints can have almost comparable roles. Variation between people in foot kinematics is high and normal. This includes variation in how specific joints move and how combinations of joints move. The foot continues to demonstrate its flexibility in enabling us to get from A to B via a large number of different kinematic solutions. Conclusion: Rather than continue to apply a poorly founded model of foot type whose basis is to make all feet meet criteria for the mechanical 'ideal' or 'normal' foot, we should embrace variation between feet and identify it as an opportunity to develop patient-specific clinical models of foot function

Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma

Cause-specific mortality patterns among hospital deaths in Thailand: validating routine death certification

Background: In Thailand, 35% of all deaths occur in hospitals, and the cause of death is medically certified by attending physicians. About 15% of hospital deaths are registered with nonspecific diagnoses, despite the potential for greater accuracy using information available from medical records. Further, issues arising from transcription of diagnoses from Thai to English at registration create uncertainty about the accuracy of registration data even for specified causes of death. This paper reports findings from a study to measure validity of registered diagnoses in a sample of deaths that occurred in hospitals in Thailand during 2005.Methods: A sample of 4,644 hospital deaths was selected, and for each case, medical records were reviewed. A process of medical record abstraction, expert physician review, and independent adjudication for the selection and coding of underlying causes of death was used to derive reference diagnoses. Validation characteristics were computed for leading causes of hospital deaths from registration data, and misclassification patterns were identified for registration diagnoses. Study findings were used to estimate cause-specific mortality patterns for hospital deaths in Thailand.Results: Adequate medical records were available for 3,316 deaths in the study sample. Losses to follow up were nondifferential by age, sex, and cause. Medical records review identified specific underlying causes for the majority of deaths that were originally assigned ill-defined causes as well as for those originally assigned to residual categories for specific cause groups. In comparison with registration data for the sample, we found an increase in the relative proportion of deaths in hospitals due to stroke, ischemic heart disease, transport accidents, HIV/AIDS, diabetes, liver diseases, and chronic obstructive pulmonary disease.Conclusions: Registration data on causes for deaths occurring in hospitals require periodic validation prior to their use for epidemiological research or public health policy. Procedures for death certification and coding of underlying causes of death need to be streamlined to improve reliability of registration data. Estimates of cause-specific mortality from this research will inform burden of disease estimation and guide interventions to reduce avoidable mortality in hospitals in Thailand

Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2-dimethylhydrazine-induced colon tumours in rats

In order to establish an optimal timing and duration of aspirin treatment in the chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats, colon tumours were induced using an established protocol and aspirin was given in the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results indicate that only aspirin treatment throughout the entire carcinogenic period significantly reduced tumour incidence and volume whereas intermittent aspirin dosing increased tumour number and/or volume, suggesting that aspirin must be used for an extended period in order to gain any chemopreventive benefit. © 1999 Cancer Research Campaig

Coexisting conical bipolar and equatorial outflows from a high-mass protostar

The BN/KL region in the Orion molecular cloud is an archetype in the study of the formation of stars much more massive than the Sun. This region contains luminous young stars and protostars, but it is difficult to study because of overlying dust and gas. Our basic expectations are shaped to some extent by the present theoretical picture of star formation, the cornerstone of which is that protostars acrete gas from rotating equatorial disks, and shed angular momentum by ejecting gas in bipolar outflows. The main source of the outflow in the BN/KL region may be an object known as radio source I, which is commonly believed to be surrounded by a rotating disk of molecular material. Here we report high-resolution observations of silicon monoxide (SiO) and water maser emission from the gas surrounding source I; we show that within 60 AU (about the size of the Solar System), the region is dominated by a conical bipolar outflow, rather than the expected disk. A slower outflow, close to the equatorial plane of the protostellar system, extends to radii of 1,000 AU.Comment: 10 pages, 2 figures. Accepted by Nature. To appear December 199

Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit

A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data. During this time period, two formal outbreaks had been declared by IPC, while WGS detected nine monophyletic clusters, seven were corroborated by epidemiological evidence and by comparison of single-nucleotide polymorphisms. One of the formal outbreaks was confirmed, and the other was not. Of the five HAdV-associated deaths, three were unlinked and the remaining two considered the source of transmission. Mixed infection was frequent (10%), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harboring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into clinical practice to influence IPC policy contemporaneously

Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV

Chronic active Epstein–Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment

Influence of the initial chemical conditions on the rational design of silica particles

The influence of the water content in the initial composition on the size of silica particles produced using the Stöber process is well known. We have shown that there are three morphological regimes defined by compositional boundaries. At low water levels (below stoichiometric ratio of water:tetraethoxysilane), very high surface area and aggregated structures are formed; at high water content (>40 wt%) similar structures are also seen. Between these two boundary conditions, discrete particles are formed whose size are dictated by the water content. Within the compositional regime that enables the classical Stöber silica, the structural evolution shows a more rapid attainment of final particle size than the rate of formation of silica supporting the monomer addition hypothesis. The clearer understanding of the role of the initial composition on the output of this synthesis method will be of considerable use for the establishment of reliable reproducible silica production for future industrial adoption