Inter-species horizontal transfer resulting in core-genome and niche-adaptive variation within Helicobacter pylori

Background Horizontal gene transfer is central to evolution in most bacterial species. The detection of exchanged regions is often based upon analysis of compositional characteristics and their comparison to the organism as a whole. In this study we describe a new methodology combining aspects of established signature analysis with textual analysis approaches. This approach has been used to analyze the two available genome sequences of H. pylori. Results This gene-by-gene analysis reveals a wide range of genes related to both virulence behaviour and the strain differences that have been relatively recently acquired from other sequence backgrounds. These frequently involve single genes or small numbers of genes that are not associated with transposases or bacteriophage genes, nor with inverted repeats typically used as markers for horizontal transfer. In addition, clear examples of horizontal exchange in genes associated with 'core' metabolic functions were identified, supported by differences between the sequenced strains, including: ftsK, xerD and polA. In some cases it was possible to determine which strain represented the 'parent' and 'altered' states for insertion-deletion events. Different signature component lengths showed different sensitivities for the detection of some horizontally transferred genes, which may reflect different amelioration rates of sequence components. Conclusion New implementations of signature analysis that can be applied on a gene-by-gene basis for the identification of horizontally acquired sequences are described. These findings highlight the central role of the availability of homologous substrates in evolution mediated by horizontal exchange, and suggest that some components of the supposedly stable 'core genome' may actually be favoured targets for integration of foreign sequences because of their degree of conservation

Fatal, unintentional drowning in older people: an assessment of the role of preexisting medical conditions

Background: The number of older people (aged 65 y and over) is increasing in Australia and chronic medical conditions are common. Aquatic activities provide physical and social benefits; however, understanding the risks related to aquatic activity is important for ongoing health and wellbeing. We explore the impact of preexisting medical conditions on unintentional fatal drowning among older people in Australia. Methods: Using coronial, forensic, and medical histories from the Australian National Coronial Information System, all cases of unintentional death by drowning (or where drowning was a factor) among older people in Australia between July 1, 2002 and June 30, 2012 were investigated. Preexisting medical conditions were reviewed to determine whether they were contributory to drowning. Results: Of the 506 older people who drowned, 69.0% had a preexisting medical condition. The leading contributory medical condition was cardiovascular disease, followed by dementia, depression, epilepsy, and Parkinson disease. All conditions except cardiovascular disease and depression were overrepresented compared with the proportion of the disease in the population. Falling into water was the most common activity immediately before drowning, especially among those with dementia, whereas those with cardiovascular disease were most likely to drown while swimming. Conclusions: Preexisting medical conditions contribute to drowning in older people but with unequal contributions. With the prevalence of medical conditions expected to increase as the population ages, targeted education for older people will be important. Risk management will enable older people to safely participate in aquatic activities

Variation in the strength of selected codon usage bias among bacteria

Among bacteria, many species have synonymous codon usage patterns that have been influenced by natural selection for those codons that are translated more accurately and/or efficiently. However, in other species selection appears to have been ineffective. Here, we introduce a population genetics-based model for quantifying the extent to which selection has been effective. The approach is applied to 80 phylogenetically diverse bacterial species for which whole genome sequences are available. The strength of selected codon usage bias, S, is found to vary substantially among species; in 30% of the genomes examined, there was no significant evidence that selection had been effective. Values of S are highly positively correlated with both the number of rRNA operons and the number of tRNA genes. These results are consistent with the hypothesis that species exposed to selection for rapid growth have more rRNA operons, more tRNA genes and more strongly selected codon usage bias. For example, Clostridium perfringens, the species with the highest value of S, can have a generation time as short as 7 min

Injured pedestrians in Cape Town - the role of alcohol

Objective. To establish a profile of injured adult pedestrians and attempt to define the role which alcohol plays in this regard. Design. Prospective survey of injured pedestrians whopresented consecutively over 9 weeks to Groote Schuur Hospital. Data on fatally injured pedestrians were retrospectively collected from the State Mortuary. Setting. Hospital-based study conducted at the trauma unit, Groote Schuur Hospital. Participants. A total of 321 pedestrians - 196 injured and 35 'dead on arrival'. Main outcome measures. Sociodemographics, blood alcohol concentration (BAC) and injury severity. Results. Patients were predominantly male and, on average, 35.6 years old. They were most frequently injured at night and over weekends. The BAC was positive in 62.1 % of pedestrians, and the mean BAC was 0.19 g/dl. Most pedestrians had at least one lower limb injury and nearly half had a head injury; however, BAC-positive pedestrians were 2.6 times more likely to have a head injury (P = 0.0009). Furthennore, BAC-positive pedestrians sustained more severe injuries, more frequently required admission to the ICU, had longer hospital admissions and were more likely to die of their injuries. The overall case fatality rate was 19.5%. Conclusions. The influence of alcohol intoxication among injured adult pedestrians in Cape Town is high, suggesting that alcohol plays a major role in these accidents. Consequently, there should be some degree of culpability in those who cross t~e road while in an intoxicated state. However, equal attention should be given to safe and convenient crossing points, good lighting and education with regard to the wearing of reflective clothing after dark.S Atr Med J 1996; 86; 1103-1105

Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study

<p>Background: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.</p> <p>Methods and Findings: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005–2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4–3.8, p<0.001) than men (2.3: 2.0–2.7, p<0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2–3.0, p<0.001) in men and 2.7 (2.2–3.4, p<0.001) in women. Between 2005–2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60–69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA1c of <7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used.</p> <p>Conclusions: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed.</p&gt

Fluticasone Propionate Protects against Ozone-Induced Airway Inflammation and Modified Immune Cell Activation Markers in Healthy Volunteers

BackgroundOzone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O3-induced airway inflammation, but their effect on innate immune activation is unknown.ObjectivesWe used a human O3 inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers.MethodsSeventeen O3-responsive subjects [> 10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O3 challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1–5 hr after the O3 challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation.ResultsFP had no effect on O3-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O3-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O3-induced modification of CD11b, mCD14, CD64, CD16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner.ConclusionsThis study confirmed and extended data demonstrating the protective effect of FP against O3-induced airway inflammation and immune cell activation

Report of Seminar on Estate Planning

Reports from the UK/CLE Seminar on Estate Planning held July 19-20, 1974

Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO_2 Fixation

Two major energy-related problems confront the world in the next 50 years. First, increased worldwide competition for gradually depleting fossil fuel reserves (derived from past photosynthesis) will lead to higher costs, both monetarily and politically. Second, atmospheric CO_2 levels are at their highest recorded level since records began. Further increases are predicted to produce large and uncontrollable impacts on the world climate. These projected impacts extend beyond climate to ocean acidification, because the ocean is a major sink for atmospheric CO2.1 Providing a future energy supply that is secure and CO_2-neutral will require switching to nonfossil energy sources such as wind, solar, nuclear, and geothermal energy and developing methods for transforming the energy produced by these new sources into forms that can be stored, transported, and used upon demand