Can oral infection be a risk factor for Alzheimer’s disease?

Alzheimer’s disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familial-onset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD)

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Self-assembly, Self-organization, Nanotechnology and vitalism

International audienceOver the past decades, self-assembly has attracted a lot of research attention and transformed the relations between chemistry, materials science and biology. The paper explores the impact of the current interest in self-assembly techniques on the traditional debate over the nature of life. The first section describes three different research programs of self-assembly in nanotechnology in order to characterize their metaphysical implications: -1- Hybridization ( using the building blocks of living systems for making devices and machines) ; -2- Biomimetics (making artifacts mimicking nature); -3- Integration (a composite of the two previous strategies). The second section focused on the elusive boundary between selfassembly and self-organization tries to map out the various positions adopted by the promoters of self-assembly on the issue of vitalism

A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

Implied cost of capital investment strategies - evidence from international stock markets

Investors can generate excess returns by implementing trading strategies based on publicly available equity analyst forecasts. This paper captures the information provided by analysts by the implied cost of capital (ICC), the internal rate of return that equates a firm's share price to the present value of analysts' earnings forecasts. We find that U.S. stocks with a high ICC outperform low ICC stocks on average by 6.0% per year. This spread is significant when controlling the investment returns for their risk exposure as proxied by standard pricing models. Further analysis across the world's largest equity markets validates these results

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Experimental properties of gluon and quark jets from a point source

Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data.Gluon jets are identified in hadronic Z0 decays as all the particles in a hemisphere opposite to a hemisphere containing two tagged quark jets. Gluon jets defined in this manner are equivalent to gluon jets produced from a color singlet point source and thus correspond to the definition employed for most theoretical calculations. In a separate stage of the analysis, we select quark jets in a manner to correspond to calculations, as the particles in hemispheres of flavor tagged light quark (uds) events. We present the distributions of rapidity, scaled energy, the logarithm of the momentum, and transverse momentum with respect to the jet axes, for charged particles in these gluon and quark jets. We also examine the charged particle multiplicity distributions of the jets in restricted intervals of rapidity. For soft particles at large transverse momentum, we observe the charged particle multiplicity ratio of gluon to quark jets to be 2.29 +- 0.09 +- 0.15 in agreement with the prediction that this ratio should approximately equal the ratio of QCD color factors, CA/CF = 2.25. The intervals used to define soft particles and large transverse momentum for this result, p<4 GeV/c and 0.8<p_t<3.0 GeV/c, are motivated by the predictions of the Herwig Monte Carlo multihadronic event generator. Additionally, our gluon jet data allow a sensitive test of the phenomenon of non-leading QCD terms known as color reconnection. We test the model of color reconnection implemented in the Ariadne Monte Carlo multihadronic event generator and find it to be disfavored by our data

Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report

BACKGROUND: Convenient once-a-week dosing has made mefloquine a popular choice as malaria prophylaxis for travel to countries with chloroquine-resistant malaria. However, the increased use of mefloquine over the past decade has resulted in reports of rare, but severe, neuropsychiatric adverse reactions, such as anxiety, depression, hallucinations and psychosis. A direct causality between mefloquine and severe reactions among travelers has been partly confounded by factors associated with foreign travel and, in the case of therapeutic doses of mefloquine, the central nervous system manifestations of Plasmodium infection itself. The present case provides a unique natural history of mefloquine-induced neuropsychiatric toxicity and revisits its dose-dependent nature. CASE PRESENTATION: This report describes an acute exacerbation of neuropsychiatric symptoms after an unwarranted therapeutic dose (1250 mg) of mefloquine in a 37-year-old male previously on a once-a-week prophylactic regimen. Neuropsychiatric symptoms began as dizziness and insomnia of several days duration, which was followed by one week of escalating anxiety and subtle alterations in behaviour. The patient's anxiety culminated into a panic episode with profound sympathetic activation. One week later, he was hospitalized after developing frank psychosis with psychomotor agitation and paranoid delusions. His psychosis remitted with low-dose quetiapine. CONCLUSION: This report suggests that an overt mefloquine-induced psychosis can be preceded by a prodromal phase of moderate symptoms such as dizziness, insomnia, and generalized anxiety. It is important that physicians advise patients taking mefloquine prophylaxis and their relatives to recognize such symptoms, especially when they are accompanied by abrupt, but subtle, changes in behaviour. Patients with a history of psychiatric illness, however minor, may be at increased risk for a mefloquine-induced neuropsychiatric toxicity. Physicians must explicitly caution patients not to self-medicate with a therapeutic course of mefloquine when a malaria diagnosis has not been confirmed