Sensitivity testing of trypanosome detection by PCR from whole blood samples using manual and automated DNA extraction methods

Automated extraction of DNA for testing of laboratory samples is an attractive alternative to labour-intensive manual methods when higher throughput is required. However, it is important to maintain the maximum detection sensitivity possible to reduce the occurrence of type II errors (false negatives; failure to detect the target when it is present), especially in the biomedical field, where PCR is used for diagnosis. We used blood infected with known concentrations of Trypanosoma copemani to test the impact of analysis techniques on trypanosome detection sensitivity by PCR. We compared combinations of a manual and an automated DNA extraction method and two different PCR primer sets to investigate the impact of each on detection levels. Both extraction techniques and specificity of primer sets had a significant impact on detection sensitivity. Samples extracted using the same DNA extraction technique performed substantially differently for each of the separate primer sets. Type I errors (false positives; detection of the target when it is not present), produced by contaminants, were avoided with both extraction methods. This study highlights the importance of testing laboratory techniques with known samples to optimise accuracy of test results

Trypanosome co-infections increase in a declining marsupial population

Understanding the impacts of parasites on wildlife is growing in importance as diseases pose a threat to wildlife populations. Woylie (syn. brush-tailed bettong, Bettongia penicillata) populations have undergone enigmatic declines in south-western Western Australia over the past decade. Trypanosomes have been suggested as a possible factor contributing towards these declines because of their high prevalence in the declining population. We asked whether temporal patterns of infection with Trypanosoma spp. were associated with the decline patterns of the host, or if other factors (host sex, body condition, co-infection or rainfall) were more influential in predicting infection patterns. Species-specific nested PCRs were used to detect the two most common trypanosomes (T. copemani and T. vegrandis) from 444 woylie blood samples collected between 2006 and 2012. Time relative to the decline (year) and an interaction with co-infection by the other trypanosome best explained patterns of infection for both trypanosomes. The prevalence of single species infections for both T. copemani and T. vegrandis was lower after the population crash, however, the occurrence of co-infections increased after the crash compared to before the crash. Our results suggest an interaction between the two parasites with the decline of their host, leading to a higher level of co-infection after the decline. We discuss the possible mechanisms that may have led to a higher level of co-infection after the population crash, and highlight the importance of considering co-infection when investigating the role of parasites in species declines

ITC EUREST-PLUS Spain: protocol of a prospective longitudinal study of smokers in Spain

Objective: The ITC EUREST-PLUS Spain Survey is a longitudinal study of a representative sample of Spanish adult (≥18 years old) smokers. This protocol describes the methods of the 2021 follow-up survey. Method: The ITC EUREST-PLUS Survey, a prospective cohort study of a representative sample of smokers in six European countries, was conducted in 2016 (baseline) and 2018 (waves 1 and 2). The 2021 ITC EUREST-PLUS Spain Survey is a continuation of the Spanish cohort with a new interview in 2021 (wave 3). Lost participants were replaced with new smokers recruited using the same multi-stage sampling design. This latest follow-up aims to examine current patterns and transitions of tobacco use and to evaluate the impact of new tobacco-related policies. Comments: The ITC EUREST-PLUS Spain Survey will provide recent information about the impact of tobacco control policies on smoking behaviour

Contraband Cigarette Purchasing from First Nation reserves in Ontario and Quebec: Findings from the 2002–2014 ITC Canada Survey

Backround: The availability of contraband cigarettes provides incentives for price-sensitive smokers to reduce their monetary costs of smoking. The objectives of this study were to examine whether Canadian smokers’ geographic proximity to First Nations reserves and attempts to quit smoking influenced the likelihood of purchasing lower-cost cigarettes from reserves. Methods: Data were from the International Tobacco Control (ITC) Canada Survey, a prospective survey of Canadian adult smokers conducted from 2002 to 2014 using telephone and online interviewing methods. Analysis was restricted to smokers from Ontario (n=2105) and Quebec (n=1427) participating in at least one survey wave. Smokers’ postal codes were used to calculate distance to the nearest reserve. Weighted logistic generalised estimating equations (GEE) regression examined the linear relationship between distance and the log odds of last purchasing cigarettes on reserve in each province. GEE models also examined the relationship between past-year quit attempts and the log odds of on-reserve purchasing. Results: Controlling for other factors, from 2002–2014, smokers from Ontario who lived 10 km closer to reserves than otherwise similar smokers had significantly higher odds of last purchasing on reserve (OR ranged from 1.16 to 1.65). Distance had little effect on smokers’ purchasing behaviours in Quebec. Moreover, in Ontario, for every 10 km increase in distance, smokers who did not try to quit had significantly greater odds of purchasing from a reserve than smokers who tried to quit (p=0.002). Conclusion: In order for tobacco taxation policies to achieve their maximal benefit, governments must limit potential sources of lower-cost cigarettes. Collaborative governance arrangements can ensure tobacco products sold on reserve to non-Indigenous people are appropriately taxed while allowing First Nations communities to keep the revenue generated by such taxes.US National Cancer Institute || Canadian Institutes of Health Research || Canadian Tobacco Control Research Initiativ

Revival of the spin-Peierls transition in Cu_xZn_(1-x)GeO_3 under pressure

Pressure and temperature dependent susceptibility and Raman scattering experiments on single crystalline Cu_xZn_(1-x)GeO_3 have shown an unusually strong increase of the spin-Peierls phase transition temperature upon applying hydrostatic pressure. The large positive pressure coefficient (7.5 K/GPa) - almost twice as large as for the pure compound (4.5 K/GPa) - is interpreted as arising due to an increasing magnetic frustration which decreases the spin-spin correlation length, and thereby weakens the influence of the non-magnetic Zn-substitution.Comment: LaTeX, 15 pages, 5 eps figures, Phys. Rev. B, to appea

Methods of the ITC Four Country Smoking and Vaping Survey, wave 1 (2016)

AIM: To describe the methods of the 2016 International Tobacco Control (ITC) Four Country Smoking and Vaping (4CV) Survey, conducted in 2016 in Australia (AU), Canada (CA), England (EN) and the United States (US). METHODS: The respondents were cigarette smokers, former smokers (quit within the previous 2 years), and at-least-weekly vapers, aged 18 years and older. Eligible cohort members from the ITC Four Country Survey (4C) were retained. New respondents were sampled by commercial firms from their panels. Where possible, ages 18-24 and vapers were oversampled. Data were collected online, and respondents were remunerated. Survey weights were calibrated to benchmarks from nationally representative surveys. RESULTS: Response rates by country for new recruits once invited ranged from 15.2 to 49.6%. Sample sizes for smokers/former smokers were 1504 in AU, 3006 in CA, 3773 in EN and 2239 in the US. Sample sizes for additional vapers were 727 in CA, 551 in EN and 494 in the US. CONCLUSION: The International Tobacco Control Four Country Smoking and Vaping Survey design and data collection methods allow analyses to examine prospectively the use of cigarettes and nicotine vaping products in jurisdictions with different regulatory policies. The effects on the sampling designs and response quality of recruiting the respondents from commercial panels are mitigated by the use of demographic and geographic quotas in sampling; by quality control measures; and by the construction of survey weights taking into account smoking/vaping status, sex, age, education and geography

Magnetic Reconnection in Extreme Astrophysical Environments

Magnetic reconnection is a basic plasma process of dramatic rearrangement of magnetic topology, often leading to a violent release of magnetic energy. It is important in magnetic fusion and in space and solar physics --- areas that have so far provided the context for most of reconnection research. Importantly, these environments consist just of electrons and ions and the dissipated energy always stays with the plasma. In contrast, in this paper I introduce a new direction of research, motivated by several important problems in high-energy astrophysics --- reconnection in high energy density (HED) radiative plasmas, where radiation pressure and radiative cooling become dominant factors in the pressure and energy balance. I identify the key processes distinguishing HED reconnection: special-relativistic effects; radiative effects (radiative cooling, radiation pressure, and Compton resistivity); and, at the most extreme end, QED effects, including pair creation. I then discuss the main astrophysical applications --- situations with magnetar-strength fields (exceeding the quantum critical field of about 4 x 10^13 G): giant SGR flares and magnetically-powered central engines and jets of GRBs. Here, magnetic energy density is so high that its dissipation heats the plasma to MeV temperatures. Electron-positron pairs are then copiously produced, making the reconnection layer highly collisional and dressing it in a thick pair coat that traps radiation. The pressure is dominated by radiation and pairs. Yet, radiation diffusion across the layer may be faster than the global Alfv\'en transit time; then, radiative cooling governs the thermodynamics and reconnection becomes a radiative transfer problem, greatly affected by the ultra-strong magnetic field. This overall picture is very different from our traditional picture of reconnection and thus represents a new frontier in reconnection research.Comment: Accepted to Space Science Reviews (special issue on magnetic reconnection). Article is based on an invited review talk at the Yosemite-2010 Workshop on Magnetic Reconnection (Yosemite NP, CA, USA; February 8-12, 2010). 30 pages, no figure

Use of molecular tools to identify patients with indolent breast cancers with ultralow risk over 2 decades

IMPORTANCE The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment. OBJECTIVE To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades. DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An indolent threshold (ultralow risk) of the US Food and Drug Administration–cleared MammaPrint 70-gene expression score was established above which no breast cancer deaths occurred after 15 years in the absence of systemic therapy. Immunohistochemical markers (n = 727 women) and Agilent microarrays, for MammaPrint risk scoring (n = 652 women), were performed from formalin-fixed paraffin-embedded primary tumor blocks. Participants were postmenopausal women with clinically detected node-negative breast cancers treated with mastectomy or lumpectomy and radiation enrolled in the Stockholm tamoxifen (STO-3) trial, 1976 to 1990. EXPOSURES After 2 years of tamoxifen vs no systemic therapy, regardless of hormone receptor status, patients without relapse who reconsented were further randomized to 3 additional years or none. MAIN OUTCOMES AND MEASURES Breast cancer–specific survival assessed by Kaplan-Meier analyses and multivariate Cox proportional hazard modeling, adjusted for treatment, patient age, year of diagnosis, tumor size, grade, hormone receptors, and ERBB2/HER2 and Ki67 status. RESULTS In this secondary analysis of node-negative postmenopausal women, conducted in the era before mammography screening, among the 652 women with MammaPrint scoring available (median age, 62.8 years of age), 377 (58%) and 275 (42%) were MammaPrint low and high risk, respectively, while 98 (15%) were ultralow risk. At 20 years, women with 70-gene high and low tumors but not ultralow tumors had a significantly higher risk of disease-specific death compared with ultralow-risk patients by Cox analysis (hazard ratios, 4.73 [95% CI, 1.38-16.22] and 4.54 [95% CI, 1.40-14.80], respectively). There were no deaths in the ultralow-risk tamoxifen-treated arm at 15 years, and these patients had a 20-year disease-specific survival rate of 97%, whereas for untreated patients the survival rate was 94%. Recursive partitioning identified ultralow risk as the most significant predictor of good outcome. In tumors “not ultralow risk,” tumor size greater than 2 cm was the most predictive of outcome. CONCLUSIONS AND RELEVANCE The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low

Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood:Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale

Items were identified that capture potential/perceived cognitive, motivational, and mood-related adverse events of MPH. The items generated will allow us to further develop and psychometrically examine their prevalence, and the extent to which they are associated with medication adherence, treatment outcome, impairment, and other reported adverse events (e.g., loss of appetite/cardiovascular effects)

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure