Isolation of polymorphic microsatellites in the stemless thistle (Cirsium acaule) and their utility in other Cirsium species

The genus Cirsium includes species with both widespread and restricted geographical distributions, several of which are serious weeds. Nine polymorphic microsatellite loci were isolated from the stemless thistle Cirsium acaule. Eight were polymorphic in C. acaule, six in C. arvense and seven in C. heterophyllum. One locus monomorphic in C. acaule showed polymorphism in C. heterophyllum. The mean number of alleles per locus was 4.1 in C. acaule, 6.2 in C. arvense and 2.9 in C. heterophyllum. These nine loci were also amplified in C. eriophorum and C. vulgare, suggesting that these markers may be of use throughout the genus

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

<p>Abstract</p> <p>Background</p> <p>Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose.</p> <p>Methods</p> <p>Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection.</p> <p>Results</p> <p>Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin.</p> <p>Conclusions</p> <p>Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.</p

Variations in HIV Prevention Coverage in Subpopulations of Australian Gay and Bisexual Men, 2017–2021: Implications for Reducing Inequities in the Combination Prevention Era

Using repeated behavioural surveillance data collected from gay and bisexual men (GBM) across Australia, we assessed trends in HIV prevention coverage (the level of ‘safe sex’ achieved in the population by the use of effective prevention methods, including condoms, pre-exposure prophylaxis [PrEP] and having an undetectable viral load). We stratified these trends by age, country of birth/recency of arrival, sexual identity, and the proportion of gay residents in the participant’s suburb. Among 25,865 participants with casual male partners, HIV prevention coverage increased from 69.8% in 2017 to 75.2% in 2021, lower than the UNAIDS target of 95%. Higher levels of coverage were achieved among older GBM (≥ 45 years), non-recently-arrived migrants, and in suburbs with ≥ 10% gay residents. The lowest levels of prevention coverage (and highest levels of HIV risk) were recorded among younger GBM (&lt; 25 years) and bisexual and other-identified participants. Younger, recently-arrived, and bisexual GBM were the most likely to use condoms, while PrEP use was concentrated among gay men, 25–44-year-olds, and in suburbs with more gay residents. The use of undetectable viral load was most common among participants aged ≥ 45 years. Our analysis shows that high HIV prevention coverage can be achieved through a mixture of condom use, PrEP use, and undetectable viral load, or by emphasising PrEP use. In the Australian context, younger, bisexual and other-identified GBM should be prioritised for enhanced access to effective HIV prevention methods. We encourage other jurisdictions to assess the level of coverage achieved by combination prevention, and variations in uptake

Double Parton Scattering Singularity in One-Loop Integrals

We present a detailed study of the double parton scattering (DPS) singularity, which is a specific type of Landau singularity that can occur in certain one-loop graphs in theories with massless particles. A simple formula for the DPS singular part of a four-point diagram with arbitrary internal/external particles is derived in terms of the transverse momentum integral of a product of light cone wavefunctions with tree-level matrix elements. This is used to reproduce and explain some results for DPS singularities in box integrals that have been obtained using traditional loop integration techniques. The formula can be straightforwardly generalised to calculate the DPS singularity in loops with an arbitrary number of external particles. We use the generalised version to explain why the specific MHV and NMHV six-photon amplitudes often studied by the NLO multileg community are not divergent at the DPS singular point, and point out that whilst all NMHV amplitudes are always finite, certain MHV amplitudes do contain a DPS divergence. It is shown that our framework for calculating DPS divergences in loop diagrams is entirely consistent with the `two-parton GPD' framework of Diehl and Schafer for calculating proton-proton DPS cross sections, but is inconsistent with the `double PDF' framework of Snigirev.Comment: 29 pages, 8 figures. Minor corrections and clarifications added. Version accepted for publication in JHE

Handheld computers for data entry: high tech has its problems too

BACKGROUND: The use of handheld computers in medicine has increased in the last decade, they are now used in a variety of clinical settings. There is an underlying assumption that electronic data capture is more accurate that paper-based data methods have been rarely tested. This report documents a study to compare the accuracy of hand held computer data capture versus more traditional paper-based methods. METHODS: Clinical nurses involved in a randomised controlled trial collected patient information on a hand held computer in parallel with a paper-based data form. Both sets of data were entered into an access database and the hand held computer data compared to the paper-based data for discrepancies. RESULTS: Error rates from the handheld computers were 67.5 error per 1000 fields, compared to the accepted error rate of 10 per 10,000 field for paper-based double data entry. Error rates were highest in field containing a default value. CONCLUSION: While popular with staff, unacceptable high error rates occurred with hand held computers. Training and ongoing monitoring are needed if hand held computers are to be used for clinical data collection

A cost effectiveness and capacity analysis for the introduction of universal rotavirus vaccination in Kenya : comparison between Rotarix and RotaTeq vaccines

Background Diarrhoea is an important cause of death in the developing world, and rotavirus is the single most important cause of diarrhoea associated mortality. Two vaccines (Rotarix and RotaTeq) are available to prevent rotavirus disease. This analysis was undertaken to aid the decision in Kenya as to which vaccine to choose when introducing rotavirus vaccination. Methods Cost-effectiveness modelling, using national and sentinel surveillance data, and an impact assessment on the cold chain. Results The median estimated incidence of rotavirus disease in Kenya was 3015 outpatient visits, 279 hospitalisations and 65 deaths per 100,000 children under five years of age per year. Cumulated over the first five years of life vaccination was predicted to prevent 34% of the outpatient visits, 31% of the hospitalizations and 42% of the deaths. The estimated prevented costs accumulated over five years totalled US$1,782,761 (direct and indirect costs) with an associated 48,585 DALYs. From a societal perspective Rotarix had a cost-effectiveness ratio of US$142 per DALY (US$5 for the full course of two doses) and RotaTeq US$288 per DALY ($10.5 for the full course of three doses). RotaTeq will have a bigger impact on the cold chain compared to Rotarix. Conclusion Vaccination against rotavirus disease is cost-effective for Kenya irrespective of the vaccine. Of the two vaccines Rotarix was the preferred choice due to a better cost-effectiveness ratio, the presence of a vaccine vial monitor, the requirement of fewer doses and less storage space, and proven thermo-stability

Long term (5 Year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial

&lt;b&gt;Background:&lt;/b&gt; Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure. &lt;br&gt;&lt;/br&gt; &lt;br&gt;&lt;/br&gt; &lt;b&gt;Methods:&lt;/b&gt; Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT. &lt;br&gt;&lt;/br&gt; &lt;br&gt;&lt;/br&gt; &lt;b&gt;Results:&lt;/b&gt; 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group. &lt;br&gt;&lt;/br&gt;&lt;br&gt;&lt;/br&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.&lt;/p&gt

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease