Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

Landmine detection and imaging using Micropower Impulse Radar (MIR)

The Lawrence Livermore National Laboratory (LLNL) has developed radar and imaging technologies with potential applications in mine detection by the armed forces and other agencies involved in determining efforts. These new technologies use a patented ultra-wideband (impulse) radar technology that is compact, low-cost, and low power. Designated as Micropower hnpulse Radar, these compact, self-contained radars can easily be assembled into arrays to form complete ground penetrating radar imaging systems. LLNL has also developed tomographic reconstruction and signal processing software capable of producing high-resolution 2-D and 3-D images of objects buried in materials like soil or concrete from radar data. Preliminary test results have shown that a radar imaging system using these technologies has the ability to image both metallic and plastic land mine surrogate targets buried in 5 to 10 cm of moist soil. In dry soil, the system can detect buried objects to a depth of 30 cm and more. This report describes our initial test results and plans for future work

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

The Dynamical Equilibrium of Galaxy Clusters

If a galaxy cluster is effectively in dynamical equilibrium then all galaxy populations within the cluster must have distributions in velocity and position that individually reflect the same underlying mass distribution, although the derived virial masses can be quite different. Specifically, within the CNOC cluster sample the virial radius of the red galaxy population is, on the average, a factor of $2.05 \pm 0.34$ smaller than that of the blue population. The red galaxies also have a smaller RMS velocity dispersion, a factor of $1.31 \pm 0.13$ within our sample. Consequently, the virial mass calculated from the blue galaxies is $3.5 \pm 1.3$ times larger than from the red galaxies. However, applying the Jeans equation of stellar-hydrodynamical equilibrium to the red and blue subsamples separately give statistically identical cluster mass profiles. This is strong evidence that these clusters are effectively equilibrium systems, and therefore empirically demonstrates that the masses in the virialized region are reliably estimated using dynamical techniques.Comment: Submitted for publication in ApJLetts. 12 pages as a uufile, also available at http://manaslu.astro.utoronto.ca/~carlberg/cnoc/br/br.ps.g

The genetic prehistory of southern Africa

Southern and eastern African populations that speak non-Bantu languages with click consonants are known to harbour some of the most ancient genetic lineages in humans, but their relationships are poorly understood. Here, we report data from 23 populations analyzed at over half a million single nucleotide polymorphisms, using a genome-wide array designed for studying human history. The southern African Khoisan fall into two genetic groups, loosely corresponding to the northwestern and southeastern Kalahari, which we show separated within the last 30,000 years. We find that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began approximately 1,200 years ago. In addition, the east African Hadza and Sandawe derive a fraction of their ancestry from admixture with a population related to the Khoisan, supporting the hypothesis of an ancient link between southern and eastern AfricaComment: To appear in Nature Communication

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

The effects of knee joint angle on neuromuscular activity during electrostimulation in healthy older adults

Introduction Electrostimulation devices stimulate the common peroneal nerve, producing a calf muscle-pump action to promote venous circulation. Whether knee joint angle influences calf neuromuscular activity remains unclear. Our aim was to determine the effects of knee joint angle on lower limb neuromuscular activity during electrostimulation. Methods Fifteen healthy, older adults underwent 60 min of electrostimulation, with the knee joint at three different angles (0°, 45° or 90° flexion; random order; 20 min each). Outcome variables included electromyography of the peroneus longus, tibialis anterior and gastrocnemius medialis and lateralis and discomfort. Results Knee angle did not influence tibialis anterior and peroneus longus neuromuscular activity during electrostimulation. Neuromuscular activity was greater in the gastrocnemius medialis (p = 0.002) and lateralis (p = 0.002) at 90°, than 0° knee angle. Electrostimulation intensity was positively related to neuromuscular activity for each muscle, with a knee angle effect for the gastrocnemius medialis (p = 0.05). Conclusion Results suggest that during electrostimulation, knee joint angle influenced gastrocnemii neuromuscular activity; increased gastrocnemius medialis activity across all intensities (at 90°), when compared to 0° and 45° flexion; and did not influence peroneus longus and tibialis anterior activity. Greater electrostimulation-evoked gastrocnemii activity has implications for producing a more forceful calf muscle-pump action, potentially further improving venous flow

Deletion of the Pichia pastoris KU70 Homologue Facilitates Platform Strain Generation for Gene Expression and Synthetic Biology

Targeted gene replacement to generate knock-outs and knock-ins is a commonly used method to study the function of unknown genes. In the methylotrophic yeast Pichia pastoris, the importance of specific gene targeting has increased since the genome sequencing projects of the most commonly used strains have been accomplished, but rapid progress in the field has been impeded by inefficient mechanisms for accurate integration. To improve gene targeting efficiency in P. pastoris, we identified and deleted the P. pastoris KU70 homologue. We observed a substantial increase in the targeting efficiency using the two commonly known and used integration loci HIS4 and ADE1, reaching over 90% targeting efficiencies with only 250-bp flanking homologous DNA. Although the ku70 deletion strain was noted to be more sensitive to UV rays than the corresponding wild-type strain, no lethality, severe growth retardation or loss of gene copy numbers could be detected during repetitive rounds of cultivation and induction of heterologous protein production. Furthermore, we demonstrated the use of the ku70 deletion strain for fast and simple screening of genes in the search of new auxotrophic markers by targeting dihydroxyacetone synthase and glycerol kinase genes. Precise knock-out strains for the well-known P. pastoris AOX1, ARG4 and HIS4 genes and a whole series of expression vectors were generated based on the wild-type platform strain, providing a broad spectrum of precise tools for both intracellular and secreted production of heterologous proteins utilizing various selection markers and integration strategies for targeted or random integration of single and multiple genes. The simplicity of targeted integration in the ku70 deletion strain will further support protein production strain generation and synthetic biology using P. pastoris strains as platform hosts