Dynamic confidence during simulated clinical tasks

Objective: Doctors' confidence in their actions is important for clinical performance. While static confidence has been widely studied, no study has examined how confidence changes dynamically during clinical tasks. Method: The confidence of novice (n = 10) and experienced (n = 10) trainee anaesthetists was measured during two simulated anaesthetic crises, bradycardia (easy task) and failure to ventilate (difficult task). Results: As expected, confidence was high in the novice and experienced groups in the easy task. What was surprising, however, was that confidence during the difficult task decreased for both groups, despite appropriate performance. Conclusions: Given that confidence affects performance, it is alarming that doctors who may be acting unsupervised should lose dynamic confidence so quickly. Training is needed to ensure that confidence does not decrease inappropriately during a correctly performed procedure. Whether time on task interacts with incorrect performance to produce further deficits in confidence should now be investigated

Acoustic Supercoupling in a Zero-Compressibility Waveguide

Funneling acoustic waves through largely mismatched channels is of fundamental importance to tailor and transmit sound for a variety of applications. In electromagnetics, zero-permittivity metamaterials have been used to enhance the coupling of energy in and out of ultranarrow channels, based on a phenomenon known as supercoupling. These metamaterial channels can support total transmission and complete phase uniformity, independent of the channel length, despite being geometrically mismatched to their input and output ports. In the field of acoustics, this phenomenon is challenging to achieve, since it requires zero-density metamaterials, typically realized with waveguides periodically loaded with membranes or resonators. Compared to electromagnetics, the additional challenge is due to the fact that conventional acoustic waveguides do not support a cut-off for the dominant mode of propagation, and therefore zero-index can be achieved only based on a collective resonance of the loading elements. Here we propose and experimentally realize acoustic supercoupling in a dual regime, using a compressibility-near-zero acoustic channel. Rather than engineering the channel with subwavelength inclusions, we operate at the cut-off of a higher-order acoustic mode, demonstrating the realization and efficient excitation of a zero-compressibility waveguide with effective soft boundaries. We experimentally verify strong transmission through a largely mismatched channel and uniform phase distribution, independent of the channel length. Our results open interesting pathways towards the realization of extreme acoustic parameters, and their implementation in relevant applications, such as ultrasound imaging, sonar technology, and sound transmission

Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas

Platinum drug-resistance in ovarian cancers is a major factor contributing to chemotherapeutic resistance of recurrent disease. Members of the Bcl-2 family such as the anti-apoptotic protein Bcl-XL have been shown to play a role in this resistance. Consequently, concurrent inhibition of Bcl-XL in combination with standard chemotherapy may improve treatment outcomes for ovarian cancer patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-XL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo\ud experimental data, wherein tumor xenografts were established in mice and treated with ABT-737 and carboplatin on a fixed periodic schedule, alone or in combination, and tumor sizes recorded regularly. We show that the validated model can be used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the time of infusion of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin administered each week combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. We also investigate the potential of ABT-737 co-therapy with carboplatin to prevent or delay the onset of carboplatin-resistance under two scenarios. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, the model is used to identify drug delivery schedules that induce tumor remission with even low doses of combination therapy. When resistance is intrinsic, due to a pre-existing cohort of resistant cells, tumor remission is no longer feasible, but our model can be used to identify dosing strategies that extend disease-free survival periods. These results underscore the potential of our model to accelerate the development of novel therapeutics such as ABT-737, by predicting optimal treatment strategies when these drugs are given in combination with currently approved cancer medications

Wound healing angiogenesis the clinical implications of a simple mathematical model

Nonhealing wounds are a major burden for health care systems worldwide. In addition, a patient who suffers from this type of wound usually has a reduced quality of life. While the wound healing process is undoubtedly complex, in this paper we develop a deterministic mathematical model, formulated as a system of partial differential equations, that focusses on an important aspect of successful healing: oxygen supply to the wound bed by a combination of diffusion from the surrounding unwounded tissue and delivery from newly-formed blood vessels. While the model equations can be solved numerically, the emphasis here is on the use of asymptotic methods to establish conditions under which new blood vessel growth can be initiated and wound-bed angiogenesis can progress. These conditions are given in terms of key model parameters including the rate of oxygen supply and its rate of consumption in the wound. We use our model to discuss the clinical use of treatments such as hyperbaric oxygen therapy, wound bed debridement, and revascularisation therapy that have the potential to initiate healing in chronic, stalled wounds

Opportunities and challenges grow from Arabidopsis genome sequencing

A recent Cold Spring Harbor Laboratory meeting in December 1997 provided the first meeting on the Arabidopsisgenome featuring a unique combination of functional studies and sequencing efforts; it included a broad range of talks covering genome sequencing and analysis efforts, mapping and defining genes, and gene expression patterns and function. Significant points to come out of the meeting were that a number of international consortiums have completed substantial portions of sequence on all five chromosomes with 17 Mb of sequence currently available through various web pages and 8 Mb of annotated sequence available through GenBank. Although physical maps of three of the five chromosomes have not yet been completed, David Bouchez (INRA, Versailles, France) reported that >90% of the clones in the CIC (CNRS, INRA, CEPH) Arabidopsis YAC library have been anchored via hybridization to genetically mapped markers. This should greatly facilitate the construction of physical maps. Michael Mindrinos from the Ausubel laboratory (Massachusetts General Hospital, Boston, MA) reported the development of a new class of PCR-based marker, the SNAPs (single nucleotideamplified polymorphisms), which should greatly assist positional cloning efforts. Daphne Preuss (University of Chicago, IL) reported the use of tetrad analysis to place the centromeres on the genetic map (Fig. 1), taking advantage of the pollen mutant quartet1 (Preuss et al. 1994; Copenhaver et al. 1998). Interestingly, this analysis placed the centromeres very close to, but not necessarily within, the centromeric repeat blocks mapped recently by Round et al. (1997)

A theoretical investigation of the effect of proliferation & adhesion on monoclonal conversion in the colonic crypt

The surface epithelium lining the intestinal tract renews itself rapidly by a coordinated programme of cell proliferation, migration and differentiation events that is initiated in the crypts of Lieberkühn. It is generally believed that colorectal cancer arises due to mutations that disrupt the normal cellular dynamics of the crypts. Using a spatially structured cell-based model of a colonic crypt, we investigate the likelihood that the progeny of a mutated cell will dominate, or be sloughed out of, a crypt. Our approach is to perform multiple simulations, varying the spatial location of the initial mutation, and the proliferative and adhesive properties of the mutant cells, to obtain statistical distributions for the probability of their domination. Our simulations lead us to make a number of predictions. The process of monoclonal conversion always occurs, and does not require that the cell which initially gave rise to the population remains in the crypt. Mutations occurring more than one to two cells from the base of the crypt are unlikely to become the dominant clone. The probability of a mutant clone persisting in the crypt is sensitive to dysregulation of adhesion. By comparing simulation results with those from a simple one-dimensional stochastic model of population dynamics at the base of the crypt, we infer that this sensitivity is due to direct competition between wild-type and mutant cells at the base of the crypt. We also predict that increases in the extent of the spatial domain in which the mutant cells proliferate can give rise to counter-intuitive, non-linear changes to the probability of their fixation, due to effects that cannot be captured in simpler models