Systematic evaluation of design choices for software development tools

[Abstract]: Most design and evaluation of software tools is based on the intuition and experience of the designers. Software tool designers consider themselves typical users of the tools that they build and tend to subjectively evaluate their products rather than objectively evaluate them using established usability methods. This subjective approach is inadequate if the quality of software tools is to improve and the use of more systematic methods is advocated. This paper summarises a sequence of studies that show how user interface design choices for software development tools can be evaluated using established usability engineering techniques. The techniques used included guideline review, predictive modelling and experimental studies with users

Evolution and Systematic Significance of Reproductive Structures in the Genus \u3cem\u3eCuscuta\u3c/em\u3e (dodders, Convolvulaceae): Pollen and Gynoecium

The genus Cuscuta (dodders, Convolvulaceae) is one of the most significant lineages of parasitic plants from economic, conservation, and anthropogenic perspectives. Members of the genus are twining stem parasites with no roots, lacking almost completely chlorophyll or its function, and gather required nutrition from their host via specialized haustorial connections. While there are almost 200 described species, problems with species identification exist because many diagnostic characters are restricted to their tiny flowers. Probably contributing to this identification difficulty is the fact that the group has not received taxonomic attention for over 75 years; even knowledge of its basic reproductive biology is sparse. Together these conditions have had negative consequences for applied research on this group. More recently, Cuscuta have witnessed a scientific rejuvenation. Molecular phylogenies have been published for 2 of the 3 major infrageneric lineages, 5 of the 15 clades of subg. Grammica have received taxonomic revisions, and work on their basic reproductive ecology has gained momentum. Still lacking, however, are reliable morphological characters that are able to support molecular phylogenies, aid in the description of new sections or species, or provide a solid morphological framework within which ecological variables can be compared. This work presents a thorough survey of the structural diversity of two of the most important, and systematically relevant, reproductive structures in Cuscuta: pollen and the gynoecium. While a number of characters were initially considered, a total of 15 qualitative and 14 quantitative characters were included in analysis. A reclassification of pollen and stigma morphology was required to better account for the variation that is present in these structures. Character states were coded using Thiele’s gap-weighting, and many of the characters were optimized onto a phylogenetic supertree that resulted from the combination of three large-scale phylogenies based on plastid trnL-F and nuclear ITS sequences. Key results are discussed in terms of their ecologic, systematic, taxonomic, cytological or developmental significance

Reply to the comment on 'Validity of certain soft photon amplitudes'

We respond to the accompanying Comment on our paper, 'Validity of certain soft photon amplitudes'. While we hope the discussion here clarifies the issues, we have found nothing which leads to a change in the original conclusions of our paper.Comment: 6 pages, Latex, uses ReVTeX, now publishe

Response by Welsh et al to letter regarding article “Urinary sodium excretion, blood pressure, and risk of future cardiovascular disease and mortality in subjects without prior cardiovascular disease”

No abstract available

Association of N-terminal pro-brain natriuretic peptide with cognitive function and depression in elderly people with type 2 diabetes

<p>Background: Type 2 diabetes mellitus is associated with risk of congestive heart failure (CHF), cognitive dysfunction and depression. CHF itself is linked both to poor cognition and depression. The ventricular N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of CHF, suggesting potential as a marker for cognitive impairment and/or depression. This was tested in the Edinburgh Type 2 Diabetes Study (ET2DS).</p> <p>Methodology and Principal Findings: Cross-sectional analysis of 1066 men and women aged 60–75 with type 2 diabetes. Results from seven neuropsychological tests were combined in a standardised general cognitive ability factor, ‘g’. A vocabulary-based test estimated pre-morbid cognitive ability. The Hospital Anxiety and Depression Scale (HADS) assessed possible depression. After adjustment for age and sex, raised plasma NT-proBNP was weakly associated with lower ‘g’ and higher depression scores (ß −0.09, 95% CI −0.13 to −0.03, p = 0.004 and ß 0.08, 95% CI 0.04 to 0.12, p<0.001, respectively). Comparing extreme quintiles of NT-proBNP, subjects in the highest quintile were more likely to have reduced cognitive ability (within the lowest tertile of ‘g’) and ‘possible’ depression (HADS depression ≥8) (OR 1.80; 95% CI: 1.20, 2.70; p = 0.005 and OR 2.18; 95% CI: 1.28, 3.71; p = 0.004, respectively). Associations persisted when pre-morbid ability was adjusted for, but as expected were no longer statistically significant following the adjustment for diabetes-related and vascular co-variates (β −0.02, 95% CI −0.07 to 0.03, p>0.05 for ‘g’; β 0.03, 95% CI −0.02 to 0.07, p>0.05 for depression scores).</p> <p>Conclusion: Raised plasma NT-proBNP was weakly but statistically significantly associated with poorer cognitive function and depression. The prospective phases of the ET2DS will help determine whether or not NT-proBNP can be considered a risk marker for subsequent cognitive impairment and incident depression and whether it provides additional information over and above traditional risk factors for these conditions.</p&gt

The Impact of Flash Glucose Monitoring on Glycaemic Control as Measured by HbA1c: A Meta-analysis of Clinical Trials and Real-World Observational Studies

Funder: Abbott Diabetes Care; doi: http://dx.doi.org/10.13039/100011946Abstract: Introduction: Glycated haemoglobin A1c (HbA1c) is the established standard measurement for assessment of glycaemic control in people with diabetes. Here we report on a meta-analysis of real-world observational studies on the impact of flash continuous glucose monitoring on glycaemic control as measured by HbA1c. Methods: A total of 271 studies were identified in our search, of which 29 contained data reporting changes in HbA1c over periods from 1 to 24 months that could be used in a statistical analysis. Our meta-analysis focuses on observed change in HbA1c at either 2, 3 or 4 months, in adult or paediatric subjects, as well as a longitudinal analysis up to 12 months in adult subjects. These data were drawn from 25 of the studies identified in our initial search. These reported HbA1c data up to 12 months in a total of 1723 participants with type 1 diabetes (T1D) or type 2 diabetes (T2D) using the FreeStyle Libre® flash glucose monitoring system. Results: Overall mean change in laboratory HbA1c across study subjects at 2–4 months was − 0.55% (95% CI − 0.70, − 0.39). Amongst the 1023 adults, mean change in HbA1c was − 0.56% (95% CI − 0.76, − 0.36); for the 447 children and adolescents, mean change in HbA1c was − 0.54% (95% CI − 0.84, − 0.23). Based on regression analysis, the degree of change in HbA1c correlated with the initial HbA1c of the study population. A longitudinal analysis in adult subjects (n = 1276) shows that HbA1c fell within the first 2 months and changes were sustained up to 12 months. No significant differences were detected between T1D and T2D. Conclusion: The meta-analysis reported here confirms that starting the FreeStyle Libre system as part of diabetes care results in a significant and sustained reduction in HbA1c for adults and children with T1D and for adults with T2D. Funding: Abbott Diabetes Care

Note: femtosecond laser micromachining of straight and linearly tapered capillary discharge waveguides

Gas-filled capillary discharge waveguides are important structures in laser-plasma interaction applications, such as the laser wakefield accelerator. We present the methodology for applying femtosecond laser micromachining in the production of capillary channels (typically 200–300 μm in diameter and 30–40 mm in length), including the formalism for capillaries with a linearly tapered diameter. The latter is demonstrated to possess a smooth variation in diameter along the length of the capillary (tunable with the micromachining trajectories). This would lead to a longitudinal plasma density gradient in the waveguide that may dramatically improve the laser-plasma interaction efficiency in applications

Back to the future: A back and forth manufacturing process journey from monoclonal antibodies to viral vectors for cell and gene therapy

The advent of new gene and cell therapies brings high promises to meet unmet medical needs. But, this also raises questions about how to produce these therapies cost effectively at scale. More specifically, producing enough high quality viral vector is key. Many early production and purification processes relied on techniques that are challenging to scale up, or are not commercially available at larger scales and sometimes even not compliant with cGMP. Scalable production and purification techniques from process development to cGMP compliant commercial manufacturing are therefore required. This feels like travelling back in time when the same challenges arose for the development of monoclonal antibodies. So instead of re-inventing the wheel, can we leverage lessons learnt from this past experience? Considering that processes for both mAbs and viral vectors include similar steps in term of cell culture, harvest, purification and formulation, the technologies developed and optimized for mAb manufacturing should therefore be applicable to viral vector processes. Here we will discuss the process similarities and differences for mAbs on one hand and adeno-associated viruses and lentiviruses on the other hand, focusing on gaps identified in developing process platforms for the production and purification of viral vectors. We will show how even the most recent advances in continuous bioprocessing for mAbs can be implemented quickly for viral vectors and the subsequent benefits generated in term of process productivity and economics