Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predomi- nantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase ‘paradigm shift’ in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and col- leagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the man- agement of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples’ dogma makes his contribution truly a genuine paradigm shift

Relating characteristics of global biodiversity targets to reported progress

To inform governmental discussions on the nature of a revised Strategic Plan for Biodiversity of the Convention on Biological Diversity (CBD), we reviewed the relevant literature and assessed the framing of the 20 Aichi Biodiversity Targets in the current strategic plan. We asked international experts from nongovernmental organizations, academia, government agencies, international organizations, research institutes, and the CBD to score the Aichi Targets and their constituent elements against a set of specific, measurable, ambitious, realistic, unambiguous, scalable, and comprehensive criteria (SMART based, excluding time bound because all targets are bound to 2015 or 2020). We then investigated the relationship between these expert scores and reported progress toward the target elements by using the findings from 2 global progress assessments (Global Biodiversity Outlook and the Intergovernmental Science‐Policy Platform on Biodiversity and Ecosystem Services). We analyzed the data with ordinal logistic regressions. We found significant positive relationships (p < 0.05) between progress and the extent to which the target elements were perceived to be measurable, realistic, unambiguous, and scalable. There was some evidence of a relationship between progress and specificity of the target elements, but no relationship between progress and ambition. We are the first to show associations between progress and the extent to which the Aichi Targets meet certain SMART criteria. As negotiations around the post‐2020 biodiversity framework proceed, decision makers should strive to ensure that new or revised targets are effectively structured and clearly worded to allow the translation of targets into actionable policies that can be successfully implemented nationally, regionally, and globally

Enhanced antipneumococcal antibody electrochemiluminescence assay: validation and bridging to the WHO reference ELISA

AIM: To re-optimize the pneumococcal (Pn) electrochemiluminescence (ECL) assay and to validate and bridge the enhanced assay to the WHO ELISA, to support the Phase III clinical trial program for V114, a 15-valent Pn conjugate vaccine. MATERIALS & METHODS: The Pn ECL assay was re-optimized, validated and formally bridged to the WHO ELISA. RESULTS: The enhanced Pn ECL assay met all prespecified validation acceptance criteria and demonstrated concordance with the WHO ELISA. The corresponding threshold value remains at 0.35 μg/ml for all 15 serotypes. CONCLUSION: The enhanced Pn ECL assay has been validated for the measurement of antibodies to 15 Pn capsular polysaccharides and is concordant with the WHO ELISA, supporting its use in clinical trials

Decision for reconstructive interventions of the upper limb in individuals with tetraplegia: the effect of treatment characteristics

Objective: To determine the effect of treatment characteristics on the\ud decision for reconstructive interventions for the upper extremities (UE) in\ud subjects with tetraplegia. - \ud Setting: Seven specialized spinal cord injury centres in the Netherlands. - \ud Method: Treatment characteristics for UE reconstructive interventions were\ud determined. Conjoint analysis (CA) was used to determine the contribution\ud and the relative importance of the treatment characteristics on the decision\ud for therapy. Therefore, a number of different treatment scenarios using these\ud characteristics were established. Different pairs of scenarios were presented\ud to subjects who were asked to choose the preferred scenario of each set. - \ud Results: forty nine subjects with tetraplegia with a stable C5, C6 or C7\ud lesion were selected. All treatment characteristics significantly influenced\ud the choice for treatment. Relative importance of treatment characteristics\ud were: intervention type (surgery or surgery with FES implant) 13%, number\ud of operations 15%, in patient rehabilitation period 22%, ambulant\ud rehabilitation period 9%, complication rate 15%, improvement of elbow\ud function 10%, improvement of hand function 15%. In deciding for therapy\ud 40% of the subjects focused on one characteristic. - \ud Conclusion: CA is applicable in Spinal Cord Injury medicine to study the\ud effect of health outcomes and non-health outcomes on the decision for\ud treatment. Non-health outcomes which relate to the intensity of treatment\ud are equally important or even more important than functional outcome in the\ud decision for reconstructive UE surgery in subjects with tetraplegia

Adenosine-mono-phosphate-activated protein kinase-independent effects of metformin in T cells

The anti-diabetic drug metformin regulates T-cell responses to immune activation and is proposed to function by regulating the energy-stress-sensing adenosine-monophosphate-activated protein kinase (AMPK). However, the molecular details of how metformin controls T cell immune responses have not been studied nor is there any direct evidence that metformin acts on T cells via AMPK. Here, we report that metformin regulates cell growth and proliferation of antigen-activated T cells by modulating the metabolic reprogramming that is required for effector T cell differentiation. Metformin thus inhibits the mammalian target of rapamycin complex I signalling pathway and prevents the expression of the transcription factors c-Myc and hypoxia-inducible factor 1 alpha. However, the inhibitory effects of metformin on T cells did not depend on the expression of AMPK in T cells. Accordingly, experiments with metformin inform about the importance of metabolic reprogramming for T cell immune responses but do not inform about the importance of AMPK

String theoretic QCD axions in the light of PLANCK and BICEP2

The QCD axion solving the strong CP problem may originate from antisymmetric tensor gauge fields in compactified string theory, with a decay constant around the GUT scale. Such possibility appears to be ruled out now by the detection of tensor modes by BICEP2 and the PLANCK constraints on isocurvature density perturbations. A more interesting and still viable possibility is that the string theoretic QCD axion is charged under an anomalous U(1)_A gauge symmetry. In such case, the axion decay constant can be much lower than the GUT scale if moduli are stabilized near the point of vanishing Fayet-Illiopoulos term, and U(1)_A-charged matter fields get a vacuum value far below the GUT scale due to a tachyonic SUSY breaking scalar mass. We examine the symmetry breaking pattern of such models during the inflationary epoch with the Hubble expansion rate 10^{14} GeV, and identify the range of the QCD axion decay constant, as well as the corresponding relic axion abundance, consistent with known cosmological constraints. In addition to the case that the PQ symmetry is restored during inflation, there are other viable scenarios, including that the PQ symmetry is broken during inflation at high scales around 10^{16}-10^{17} GeV due to a large Hubble-induced tachyonic scalar mass from the U(1)_A D-term, while the present axion scale is in the range 10^{9}-5\times 10^{13} GeV, where the present value larger than 10^{12} GeV requires a fine-tuning of the axion misalignment angle. We also discuss the implications of our results for the size of SUSY breaking soft masses.Comment: 29 pages, 1 figure; v3: analysis updated including the full anharmonic effects, references added, version accepted for publication in JHE

Centre symmetric 3d effective actions for thermal SU(N) Yang-Mills from strong coupling series

We derive three-dimensional, Z(N)-symmetric effective actions in terms of Polyakov loops by means of strong coupling expansions, starting from thermal SU(N) Yang-Mills theory in four dimensions on the lattice. An earlier action in the literature, corresponding to the (spatial) strong coupling limit, is thus extended by several higher orders, as well as by additional interaction terms. We provide analytic mappings between the couplings of the effective theory and the parameters $N_\tau,\beta$ of the original thermal lattice theory, which can be systematically improved. We then investigate the deconfinement transition for the cases SU(2) and SU(3) by means of Monte Carlo simulations of the effective theory. Our effective models correctly reproduce second order 3d Ising and first order phase transitions, respectively. Furthermore, we calculate the critical couplings $\beta_c(N_\tau)$ and find agreement with results from simulations of the 4d theory at the few percent level for $N_\tau=4-16$.Comment: 27 pages, 21 figures; final version published in JHEP; attached the corresponding Erratum (ref. JHEP 1107:014,2011, DOI 10.1007/JHEP07(2011)014) for ease of consultatio