Assessing differential attrition in clinical trials: self-monitoring of oral anticoagulation and type II diabetes

Background: Analyzing drop out rates and when they occur may give important information about the patient characteristics and trial characteristics that affect the overall uptake of an intervention. Methods: We searched Medline and the Cochrane library from the beginning of the databases to May 2006 for published systematic reviews that compared the effects of self-monitoring (self-testing) or self-management (self-testing and self-dosage) of oral anticoagulation or self-monitored blood glucose in type 2 diabetics who were not using insulin. We assessed all study withdrawals pre-randomization and post randomization and sought information on the reasons for discontinuation of all participants. To measure the differential between groups in attrition we used the relative attrition (RA), which is equivalent to relative risk but uses attrition as the outcome (i.e. attrition in intervention group/ attrition in control group). We determined the percentage drop outs for control and intervention groups and used DerSimonian and Laird random effects models to estimate a pooled relative attrition. L'abbe type plots created in R (version 2.0.2) were used to represent the difference in the relative attrition among the trials with 95% confidence areas and weights derived from the random effects model. Results: With self-monitoring of blood glucose in type 2 diabetes, attrition ranged from 2.3% to 50.0% in the intervention groups and 0% to 40.4% in the control groups. There was no significant difference between the intervention and control, with an overall RA of 1.18 [95% CI, 0.70-2.01]. With self-monitoring of oral anticoagulation attrition ranged from 0% to 43.2% in the intervention groups, and 0% to 21.4% in the control group. The RA was significantly greater in the intervention group, combined RA, 6.05 [95% CI, 2.53-14.49]. Conclusion: This paper demonstrates the use of relative attrition as a new tool in systematic review methodology which has the potential to identify patient, intervention and trial characteristics which influences attrition in trials

Chemical and physical variations of cannabis smoke from a variety of cannabis samples in New Zealand

Studies have compared the chemical properties of tobacco smoke to those of cannabis smoke, with the objective of identifying the chemical attributes responsible for the mutagenicity and carcinogenicity of cannabis smoke. Comparative studies have included small sample sizes and produced conflicting results. The aim of this study was to assess the major chemical and physical variations of cannabis smoke across a range of cannabis samples of different potencies and origins, sourced from the illegal market in New Zealand. Twelve cannabis samples were studied ranging from 1.0% to 13.4% delta-9-tetrahydrocannabinol (D9THC) content. A smoking machine was used to smoke “joints” (cannabis cigarettes) and the chemical/physical properties of the smoke assessed. The chemical constituents of the smoke extracts were analysed by gas chromatography/mass spectrometry. A range of different chemical constituents (in addition to D9THC) were identified and their concentrations estimated. Terpenoids were identified as the major variable in cannabis smoke, showing a 40-fold range in total terpenoid content. Analysis of the total particulate matter showed that significantly different levels of particulate matter were produced between the different cannabis samples, ranging from 14.6 to 66.3 mg/g of cannabis smoked. The D9THC delivery efficiency during smoking was also investigated and produced consistent results showing a mean and median of 12.6% and 10.8%, respectively, of the theoretically available D9THC (ranging from 7.2% to 28.0%)

On differences in the equation-of-state for a selection of seven representative mammalian tissue analogue materials

Tissue analogues employed for ballistic purposes are often monolithic in nature, e.g. ballistic gelatin and soap, etc. However, such constructs are not representative of real-world biological systems. Further, ethical considerations limit the ability to test with real-world tissues. This means that availability and understanding of accurate tissue simulants is of key importance. Here, the shock response of a wide range of ballistic simulants (ranging from dermal (protective / bulk) through to skeletal simulant materials) determined via plate-impact experiments are discussed, with a particular focus on the classification of the behaviour of differing simulants into groups that exhibit a similar response under high strain-rate loading. Resultant Hugoniot equation-of-state data (Us-up; P-v) provides appropriate feedstock materials data for future hydrocode simulations of ballistic impact events

Evaporation, seepage and water quality management in storage dams: a review of research methods

One of the most significant sources of water wastage in Australia is loss from small storage dams, either by seepage or evaporation. Over much of Australia, evaporative demand routinely exceeds precipitation. This paper outlines first, methodologies and measurement techniques to quantify the rate of evaporative loss from fresh water storages. These encompass high-accuracy water balance monitoring; determination of the validity of alternative estimation equations, in particular the FAO56 Penman- Monteith ETo methodology; and the commencement of CFD modeling to determine a 'dam factor' in relation to practical atmospheric measurement techniques. Second, because the application of chemical monolayers is the only feasible alternative to the high cost of physically covering the storages to retard evaporation, the use of cetyl alcohol-based monolayers is reviewed, and preliminary research on their degradation by photolytic action, by wind break-up and by microbial degradation reported. Similarly, preliminary research on monolayer visualisation techniques for field application is reported; and potential enhancement of monolayers by other chemicals and attendant water quality issues are considered

Observed impacts of COVID-19 on urban CO₂ emissions

Governments restricted mobility and effectively shuttered much of the global economy in response to the COVID‐19 pandemic. Six San Francisco Bay Area counties were the first region in the United States to issue a “shelter‐in‐place” order asking non‐essential workers to stay home. Here we use CO₂ observations from 35 Berkeley Environment, Air‐quality and CO₂ Network (BEACO₂N) nodes and an atmospheric transport model to quantify changes in urban CO₂ emissions due to the order. We infer hourly emissions at 900‐m spatial resolution for 6 weeks before and 6 weeks during the order. We observe a 30% decrease in anthropogenic CO₂ emissions during the order and show that this decrease is primarily due to changes in traffic (–48%) with pronounced changes to daily and weekly cycles; non‐traffic emissions show small changes (–8%). These findings provide a glimpse into a future with reduced CO₂ emissions through electrification of vehicles

Observed impacts of COVID-19 on urban CO₂ emissions

Governments restricted mobility and effectively shuttered much of the global economy in response to the COVID‐19 pandemic. Six San Francisco Bay Area counties were the first region in the United States to issue a “shelter‐in‐place” order asking non‐essential workers to stay home. Here we use CO₂ observations from 35 Berkeley Environment, Air‐quality and CO₂ Network (BEACO₂N) nodes and an atmospheric transport model to quantify changes in urban CO₂ emissions due to the order. We infer hourly emissions at 900‐m spatial resolution for 6 weeks before and 6 weeks during the order. We observe a 30% decrease in anthropogenic CO₂ emissions during the order and show that this decrease is primarily due to changes in traffic (–48%) with pronounced changes to daily and weekly cycles; non‐traffic emissions show small changes (–8%). These findings provide a glimpse into a future with reduced CO₂ emissions through electrification of vehicles

Pressure tolerance of Artemia cysts compressed in water medium

The high pressure tolerance of cysts of Artemia salina was investigated up to several GPa in water. No survival was observed after exposure to 1.0 GPa for 15 min. After exposure to 2.0 GPa for the same time duration, the hatching rate had recovered to 33%, but decreased to 8% following compression at 7.5 GPa. This contrasts with results using Fluorinert™ as the pressure-transmitting medium where 80–88% recovery was observed. The lower survival rate in water is accompanied by swelling of the eggs, indicating that liquid H2O close to the ice-VI crystallization pressure penetrated inside the eggs. This pressure exceeds the stability limit for proteins and other key biomolecules components within the embryos that could not be resuscitated. Rehydration takes several minutes and so was not completed for all samples compressed to higher pressures, prior to ice-VI formation, resulting in renewed survival. However H2O penetration inside the shell resulted in increased mortalit

Fast and accurate modelling of longitudinal and repeated measures neuroimaging data

Despite the growing importance of longitudinal data in neuroimaging, the standard analysis methods make restrictive or unrealistic assumptions (e.g., assumption of Compound Symmetry—the state of all equal variances and equal correlations—or spatially homogeneous longitudinal correlations). While some new methods have been proposed to more accurately account for such data, these methods are based on iterative algorithms that are slow and failure-prone. In this article, we propose the use of the Sandwich Estimator (SwE) method which first estimates the parameters of interest with a simple Ordinary Least Square model and second estimates variances/covariances with the “so-called” SwE which accounts for the within-subject correlation existing in longitudinal data. Here, we introduce the SwE method in its classic form, and we review and propose several adjustments to improve its behaviour, specifically in small samples. We use intensive Monte Carlo simulations to compare all considered adjustments and isolate the best combination for neuroimaging data. We also compare the SwE method to other popular methods and demonstrate its strengths and weaknesses. Finally, we analyse a highly unbalanced longitudinal dataset from the Alzheimer's Disease Neuroimaging Initiative and demonstrate the flexibility of the SwE method to fit within- and between-subject effects in a single model. Software implementing this SwE method has been made freely available at http://warwick.ac.uk/tenichols/SwE

Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection

Background and aims: CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. Methods: A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. Results: A strong 'HLA footprint' in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9/12) compared with the control group (1/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6/12) compared with controls (2/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03- positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. Conclusions: It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent viruses, with important implications for HCV vaccine studies