Clinical applications of high-intensity focused ultrasound

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Using discrete choice experiments to investigate subject preferences for preventive asthma medication

Background and objective: Long-term adherence to inhaled corticosteroids is poor despite the crucial role of preventer medications in achieving good asthma outcomes. This study was undertaken to explore patient preferences in relation to their current inhaled corticosteroid medication, a hypothetical preventer or no medication. Methods: A discrete choice experiment was conducted in 57 adults with mild-moderate asthma and airway hyper-responsiveness, who were using inhaled corticosteroid ≤500 μg/day (beclomethasone equivalent). In the discrete choice experiment, subjects evaluated 16 hypothetical scenarios made up of 10 attributes that described the process and outcomes of taking asthma medication, with two to four levels for each attribute. For each scenario, subjects chose between the hypothetical medication, the medication they were currently taking and no asthma medication. A random parameter multinomial logit model was estimated to quantify subject preferences for the aspects of taking asthma medication and the influence of attributes on medication decisions. Results: Subjects consistently made choices in favour of being able to do strenuous and sporting activities with or without reliever, experiencing no side-effects and never having to monitor their peak flow. Frequency of collecting prescriptions, frequency of taking the medication, its route of administration and the strength of the doctor recommendation about the medication were not significant determinants of choice. Conclusions: The results of this study suggest that patients prefer a preventer that confers capacity to maximize physical activity, has no side-effects and does not require daily peak flow monitoring. © 2007 The Authors

Tolerance of high-intensity focused ultrasound ablation in patients with hepatocellular carcinoma

BACKGROUND: High-intensity focused ultrasound (HIFU) ablation is a relatively new, noninvasive way of ablation for treating hepatocellular carcinoma (HCC). Emerging evidence has shown that it is effective for the treatment of HCC, even in patients with poor liver function. There is currently no data on the safety limit of HIFU ablation in patients with cirrhosis. However, this information is vital for the selection of appropriate patients for the procedure. We analyzed HCC patients who had undergone HIFU ablation and determined the lower limit of liver function and other patient factors with which HCC patients can tolerate this treatment modality. METHODS: Preoperative variables of 100 patients who underwent HIFU ablation for HCC were analyzed to identify the risk factors in HIFU intolerance in terms of stress-induced complications. Factors that may contribute to postablation complications were compared. RESULTS: Thirteen (13 %) patients developed a total of 18 complications. Morbidity was mainly due to skin and subcutaneous tissue injuries (n = 9). Five patients had first-degree skin burn, one had second-degree skin burn, and three had third-degree skin burn. Four complications were grade 3a in the Clavien classification and 14 were below this grade. Univariate analysis showed that age (p = 0.022) was the only independent factor in HIFU intolerance. CONCLUSIONS: HIFU ablation is generally well tolerated in HCC patients with cirrhosis. It is safe for Child-Pugh A and B patients and selected Child-Pugh C patients. With this new modality, HCC patients who were deemed unsalvageable by other surgical means in the past because of simultaneous Child-Pugh B or C disease now have a new hope.published_or_final_versio

Assessment of learning curves in complex surgical interventions: a consecutive case-series study

Background: Surgical interventions are complex, which complicates their rigorous assessment through randomised clinical trials. An important component of complexity relates to surgeon experience and the rate at which the required level of skill is achieved, known as the learning curve. There is considerable evidence that operator performance for surgical innovations will change with increasing experience. Such learning effects complicate evaluations; the start of the trial might be delayed, resulting in loss of surgeon equipoise or, if an assessment is undertaken before performance has stabilised, the true impact of the intervention may be distorted. Methods: Formal estimation of learning parameters is necessary to characterise the learning curve, model its evolution and adjust for its presence during assessment. Current methods are either descriptive or model the learning curve through three main features: the initial skill level, the learning rate and the final skill level achieved. We introduce a fourth characterising feature, the duration of the learning period, which provides an estimate of the point at which learning has stabilised. We propose a two-phase model to estimate formally all four learning curve features. Results: We demonstrate that the two-phase model can be used to estimate the end of the learning period by incorporating a parameter for estimating the duration of learning. This is achieved by breaking down the model into a phase describing the learning period and one describing cases after the final skill level is reached, with the break point representing the length of learning. We illustrate the method using cardiac surgery data. Conclusions: This modelling extension is useful as it provides a measure of the potential cost of learning an intervention and enables statisticians to accommodate cases undertaken during the learning phase and assess the intervention after the optimal skill level is reached. The limitations of the method and implications for the optimal timing of a definitive randomised controlled trial are also discussed

A frameshift mutation of the chloroplast matK coding region is associated with chlorophyll deficiency in the Cryptomeria japonica virescent mutant Wogon-Sugi

Wogon-Sugi has been reported as a cytoplasmically inherited virescent mutant selected from a horticultural variety of Cryptomeria japonica. Although previous studies of plastid structure and inheritance indicated that at least some mutations are encoded by the chloroplast genome, the causative gene responsible for the primary chlorophyll deficiency in Wogon-Sugi, has not been identified. In this study, we identified this gene by genomic sequencing of chloroplast DNA and genetic analysis. Chloroplast DNA sequencing of 16 wild-type and 16 Wogon-Sugi plants showed a 19-bp insertional sequence in the matK coding region in the Wogon-Sugi. This insertion disrupted the matK reading frame. Although an indel mutation in the ycf1 and ycf2 coding region was detected in Wogon-Sugi, sequence variations similar to that of Wogon-Sugi were also detected in several wild-type lines, and they maintained the reading frame. Genetic analysis of the 19 bp insertional mutation in the matK coding region showed that it was found only in the chlorophyll-deficient sector of 125 full-sibling seedlings. Therefore, the 19-bp insertion in the matK coding region is the most likely candidate at present for a mutation underlying the Wogon-Sugi phenotype

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

Reality TV as a trigger of everyday political talk in the net-based public sphere

It is news journalism that is commonly considered the practice that reports on the political and invites us to act as citizens. However, there are other media genres, forms and content that may provoke the citizen in us. They not only provide talking points but also facilitate communicative spaces whereby active audiences transform into deliberating publics by bridging their knowledge, identities and experiences to society through everyday, informal political talk. The internet provides a public space whereby this everyday-life politicization can occur bottom-up. This article addresses this process of politicization in the context of political talk and discusses the boundaries between private and public by examining how it emerges in forums dedicated to British popular reality TV programmes. The article pays particular attention to the shift from non-political talk to the lifestyle-based political issues and the more conventional political topics that arise, and explores the triggers of such talk

Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine

Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use of tissue-engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell-seeded, decellularized tissue-engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal stenosis after conventional reconstructive techniques failed. The graft represents the first cell-seeded tracheal graft manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and clinical data from the case, which ended in the death of the recipient. Early results were encouraging, but an acute event, hypothesized to be an intrathoracic bleed, caused sudden airway obstruction 3 weeks post-transplantation, resulting in her death. We detail the clinical events and identify areas of priority to improve future grafts. In particular, we advocate the use of stents during the first few months post-implantation. The negative outcome of this case highlights the inherent difficulties in clinical translation where preclinical in vivo models cannot replicate complex clinical scenarios that are encountered. The practical difficulties in delivering GMP grafts underscore the need to refine protocols for phase I clinical trials

Viroids: survivors from the RNA world?

[EN] Because RNA can be a carrier of genetic information and a biocatalyst, there is a consensus that it emerged before DNA and proteins, which eventually assumed these roles and relegated RNA to intermediate functions. If such a scenario¿the so-calledRNAworld¿existed,wemight hope to find its relics in our presentworld. The properties of viroids that make them candidates for being survivors of the RNA world include those expected for primitive RNA replicons: (a) small size imposed by error-prone replication, (b) high G + C content to increase replication fidelity, (c) circular structure for assuring complete replication without genomic tags, (d ) structural periodicity for modular assembly into enlarged genomes, (e) lack of protein-coding ability consistent with a ribosome-free habitat, and ( f ) replication mediated in some by ribozymes, the fingerprint of the RNA world. With the advent of DNA and proteins, those protoviroids lost some abilities and became the plant parasites we now know.R.F. has received funding by grant BFU2011-28443 from Ministerio de Economia y Competititvidad (MINECO, Spain), R.S. by grants BFU2011-25271 (MINECO) and ERC-2011-StG-281191-VIRMUT (European Research Council), and S.F.E. by grant BFU2012-30805 (MINECO). P.S. has been supported by postdoctoral contracts from Generalitat Valenciana (APOSTD/2010, program VALi+d) and MINECO (program Juan de la Cierva).Flores Pedauye, R.; Gago Zachert, SP.; Serra Alfonso, P.; Sanjuan Verdeguer, R.; Elena Fito, SF. (2014). Viroids: survivors from the RNA world?. Annual Review of Microbiology. 68:395-414. https://doi.org/10.1146/annurev-micro-091313-103416S3954146