31 research outputs found
Antibiotic research and development: business as usual?
This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner
Does electronic decision support influence advanced life support in simulated cardiac arrest?
Introduction: In-hospital cardiac arrest is common but survival rates vary considerably. The reasons for this may relate to human factors. Decision support systems and tools have been suggested as a means of reducing human errors and improving outcomes.
Methods: This study aimed to: investigate if an electronic decision support system (eDSS) influenced advanced life support (ALS) in a simulated in-hospital cardiac arrest scenario; and explore practitioners' views of their performance with and without the eDSS. Teams of nurses and student nurses managed two scenarios with and without using an eDSS, and their adherence to an ALS protocol was assessed. Teams then took part in group interviews.
Results: Teams using the eDSS were more likely to adhere to the drug and shock administration elements of the ALS protocol but were less safe in doing so, which may have been because they were unfamiliar with it. The interviews yielded one overarching theme—team working—and three subthemes of team performance and dynamics, team leader performance and areas for development. Some considered the eDSS as a source of reassurance that supported organisation and communication, while others found it a distraction; reduced situational awareness was observed when it was used.
Conclusion: While an eDSS can support practitioners managing a simulated cardiac arrest, it is important to test prototypes in extensive simulation-based situations before they are used in clinical practice
Engineering of microfabricated ion traps and integration of advanced on-chip features
Atomic ions trapped in electromagnetic potentials have long been used for fundamental studies in quantum physics. Over the past two decades, trapped ions have been successfully used to implement technologies such as quantum computing, quantum simulation, atomic clocks, mass spectrometers and quantum sensors. Advanced fabrication techniques, taken from other established or emerging disciplines, are used to create new, reliable ion-trap devices aimed at large-scale integration and compatibility with commercial fabrication. This Technical Review covers the fundamentals of ion trapping before discussing the design of ion traps for the aforementioned applications. We overview the current microfabrication techniques and the various considerations behind the choice of materials and processes. Finally, we discuss current efforts to include advanced, on-chip features in next-generation ion traps
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Determining the Composition and Stability of Protein Complexes Using an Integrated Label-Free and Stable Isotope Labeling Strategy
In biological systems, proteins catalyze the fundamental reactions that underlie all cellular functions, including metabolic processes and cell survival and death pathways. These biochemical reactions are rarely accomplished alone. Rather, they involve a concerted effect from many proteins that may operate in a directed signaling pathway and/or may physically associate in a complex to achieve a specific enzymatic activity. Therefore, defining the composition and regulation of protein complexes is critical for understanding cellular functions. In this chapter, we describe an approach that uses quantitative mass spectrometry (MS) to assess the specificity and the relative stability of protein interactions. Isolation of protein complexes from mammalian cells is performed by rapid immunoaffinity purification, and followed by in-solution digestion and high-resolution mass spectrometry analysis. We employ complementary quantitative MS workflows to assess the specificity of protein interactions using label-free MS and statistical analysis, and the relative stability of the interactions using a metabolic labeling technique. For each candidate protein interaction, scores from the two workflows can be correlated to minimize nonspecific background and profile protein complex composition and relative stability
A qualitative assessment of the acceptability of hepatitis C remote self-testing and self-sampling amongst people who use drugs in London, UK
Factors obstetricians, family physicians and midwives consider when counselling women about a trial of labour after caesarean and planned repeat caesarean: a qualitative descriptive study
The role of versican G3 domain in regulating breast cancer cell motility including effects on osteoblast cell growth and differentiation <it>in vitro</it> – evaluation towards understanding breast cancer cell bone metastasis
<p>Abstract</p> <p>Background</p> <p>Versican is detected in the interstitial tissues at the invasive margins of breast carcinoma, is predictive of relapse, and negatively impacts overall survival rates. The versican G3 domain is important in breast cancer cell growth, migration and bone metastasis. However, mechanistic studies evaluating versican G3 enhanced breast cancer bone metastasis are limited.</p> <p>Methods</p> <p>A versican G3 construct was exogenously expressed in the 66c14 and the MC3T3-E1 cell line. Cells were observed through light microscopy and viability analyzed by Coulter Counter or determined with colorimetric proliferation assays. The Annexin V-FITC apoptosis detection kit was used to detect apoptotic activity. Modified Chemotactic Boyden chamber migration invasion assays were applied to observe tumor migration and invasion to bone stromal cells and MC3T3-E1 cells. Alkaline phosphatase (ALP) staining and ALP ELISA assays were performed to observe ALP activity in MC3T3-E1 cells.</p> <p>Results</p> <p>In the four mouse breast cancer cell lines 67NR, 66c14, 4T07, and 4T1, 4T1 cells expressed higher levels of versican, and showed higher migration and invasion ability to MC3T3-E1 cells and primary bone stromal cells. 4T1 conditioned medium (CM) inhibited MC3T3-E1 cell growth, and even lead to apoptosis. Only 4T1 CM prevented MC3T3-E1 cell differentiation, noted by inhibition of alkaline phosphatase (ALP) activity. We exogenously expressed a versican G3 construct in a cell line that expresses low versican levels (66c14), and observed that the G3-expressing 66c14 cells showed enhanced cell migration and invasion to bone stromal and MC3T3-E1 cells. This observation was prevented by selective EGFR inhibitor AG1478, selective MEK inhibitor PD 98059, and selective AKT inhibitor Triciribine, but not by selective JNK inhibitor SP 600125. Versican G3 enhanced breast cancer cell invasion to bone stromal cells or osteoblast cells appears to occur through enhancing EGFR/ERK or AKT signaling. G3 expressing MC3T3-E1 cells showed inhibited cell growth and cell differentiation when cultured with TGF-β1 (1 ng/ml), and expressed enhanced cell apoptosis when cultured with TNF-α (2 ng/ml). Enhanced EGFR/JNK signaling appears to be responsible for G3 enhanced osteoblast apoptosis and inhibited osteoblast differentiation. Whereas repressed expression of GSK-3β (S9P) contributes to G3 inhibited osteoblast growth. Versican G3 functionality was dependent on its EGF-like motifs. Without the structure of EGF-like repeats, the G3 domain would not confer enhancement of tumor cell migration and invasion to bone with concordant inhibition of osteoblast differentiation and promotion of osteoblast apoptosis.</p> <p>Conclusions</p> <p>Versican enhances breast cancer bone metastasis not only through enhancing tumor cell mobility, invasion, and survival in bone tissues, but also by inhibiting pre-osteoblast cell growth, differentiation, which supply favorable microenvironments for tumor metastasis.</p