Acromegaly, Mr Punch and caricature.

The origin of Mr Punch from the Italian Pulcinella of the Commedia dell'arte is well known but his feature, large hooked nose, protruding chin, kyphosis and sternal protrusion all in an exaggerated form also suggest the caricature of an acromegalic. This paper looks at the physical characteristics of acromegaly, the origin of Mr Punch and the development of caricature linking them together in the acromegalic caricature that now has a life of its own

Effectiveness and toxicity of lenvatinib in refractory thyroid cancer:Dutch real-life data

Objective: The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods: From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. Results: A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade >= 3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0-15.5) and 18.3 (95% CI: 4.9-31.7) months, respectively, response rate was 38% (95% CI: 23-54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions: PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account

Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes

Background The ParaHox gene cluster is the evolutionary sister to the Hox cluster. Whilst the role of the Hox cluster in patterning the anterior-posterior axis of bilaterian animals is well established, and the organisation of vertebrate Hox clusters is intimately linked to gene regulation, much less is known about the more recently discovered ParaHox cluster. ParaHox gene clustering, and its relationship to expression, has only been described in deuterostomes. Conventional protostome models (Drosophila melanogaster and Caenorhabditis elegans) are secondarily derived with respect to ParaHox genes, suffering gene loss and cluster break-up. Results We provide the first evidence for ParaHox gene clustering from a less-derived protostome animal, the annelid Platynereis dumerilii. Clustering of these genes is thus not a sole preserve of the deuterostome lineage within Bilateria. This protostome ParaHox cluster is not entirely intact however, with Pdu-Cdx being on the opposite end of the same chromosome arm from Pdu-Gsx and Pdu-Xlox. From the genomic sequence around the P. dumerilii ParaHox genes the neighbouring genes are identified, compared with other taxa, and the ancestral arrangement deduced. Conclusion We relate the organisation of the ParaHox genes to their expression, and from comparisons with other taxa hypothesise that a relatively complex pattern of ParaHox gene expression existed in the protostome-deuterostome ancestor, which was secondarily simplified along several invertebrate lineages. Detailed comparisons of the gene content around the ParaHox genes enables the reconstruction of the genome surrounding the ParaHox cluster of the protostome-deuterostome ancestor, which existed over 550 million years ago.Publisher PDFPeer reviewe

Transport and elastic scattering times as probes of the nature of impurity scattering in single and bilayer graphene

Both transport $\tau_{tr}$ and elastic scattering times $\tau_{e}$ are experimentally determined from the carrier density dependence of the magnetoconductance of monolayer and bilayer graphene. Both times and their dependences in carrier density are found to be very different in the monolayer and the bilayer. However their ratio $\tau_{tr}/\tau_{e}$is found to be of the order of $1.5$ in both systems and independent of the carrier density. These measurements give insight on the nature (neutral or charged) and spatial extent of the scattering centers. Comparison with theoretical predictions yields that the main scattering mechanism in our graphene samples could be due to strong scatterers of short range, inducing resonant scattering, a likely candidate being vacancies

Assessment of the potential in vivo ecotoxicity of Double-Walled Carbon Nanotubes (DWNTs) in water, using the amphibian Ambystoma mexicanum

Because of their specific properties (mechanical, electrical, etc), carbon nanotubes (CNTs) are being assessed for inclusion in many manufactured products. Due to their massive production and number of potential applications, the impact of CNTs on the environment must be taken into consideration. The present investigation evaluates the ecotoxic potential of CNTs in the amphibian larvae (Ambystoma mexicanum). Acute toxicity and genotoxicity were analysed after 12 days of exposure in laboratory conditions. The genotoxic effects were analysed by scoring the micronucleated erythrocytes in the circulating blood of the larvae according to the French standard micronucleus assay. The results obtained in the present study demonstrated that CNTs are neither acutely toxic nor genotoxic to larvae whatever the CNTs concentration in the water, although black masses of CNTs were observed inside the gut. In the increasing economical context of CNTs, complementary studies must be undertaken, especially including mechanistic and environmental investigations

Dispersively detected Pauli Spin-Blockade in a Silicon Nanowire Field-Effect Transistor

We report the dispersive readout of the spin state of a double quantum dot formed at the corner states of a silicon nanowire field-effect transistor. Two face-to-face top-gate electrodes allow us to independently tune the charge occupation of the quantum dot system down to the few-electron limit. We measure the charge stability of the double quantum dot in DC transport as well as dispersively via in-situ gate-based radio frequency reflectometry, where one top-gate electrode is connected to a resonator. The latter removes the need for external charge sensors in quantum computing architectures and provides a compact way to readout the dispersive shift caused by changes in the quantum capacitance during interdot charge transitions. Here, we observe Pauli spin-blockade in the high-frequency response of the circuit at finite magnetic fields between singlet and triplet states. The blockade is lifted at higher magnetic fields when intra-dot triplet states become the ground state configuration. A lineshape analysis of the dispersive phase shift reveals furthermore an intradot valley-orbit splitting $\Delta_{vo}$ of 145 $\mu$eV. Our results open up the possibility to operate compact CMOS technology as a singlet-triplet qubit and make split-gate silicon nanowire architectures an ideal candidate for the study of spin dynamics

Study protocol for the safety and efficacy of probiotic therapy on days alive and out of hospital in adult ICU patients: The multicentre, randomised, placebo-controlled Restoration Of gut microflora in Critical Illness Trial (ROCIT)

Introduction The effect of early and sustained administration of daily probiotic therapy on patients admitted to the intensive care unit (ICU) remains uncertain. Methods and analysis The Restoration Of gut microflora in Critical Illness Trial (ROCIT) study is a multicentre, randomised, placebo-controlled, parallel-group, two-sided superiority trial that will enrol 220 patients in five ICUs. Adult patients who are within 48 hours of admission to an ICU and are expected to require intensive care beyond the next calendar day will be randomised in a 1:1 ratio to receive early and sustained Lactobacillus plantarum 299v probiotic therapy in addition to usual care or placebo in addition to usual care. The primary endpoint is days alive and out of hospital to day 60. Ethics and dissemination ROCIT has been approved by the South Metropolitan Health Service Human Research Ethics Committee (ref: RGS00000004) and the St John of God Health Care Human Research Ethics Committee (ref: 1183). The trial results will be submitted for publication in a peer-reviewed journal. Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTR12617000783325); Pre-results

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Achieving global biodiversity goals by 2050 requires urgent and integrated actions

Governments are negotiating actions intended to halt biodiversity loss and put it on a path to recovery by 2050. Here, we show that bending the curve for biodiversity is possible, but only if actions are implemented urgently and in an integrated manner. Connecting these actions to biodiversity outcomes and tracking progress remain a challenge

Are Hox Genes Ancestrally Involved in Axial Patterning? Evidence from the Hydrozoan Clytia hemisphaerica (Cnidaria)

Background: The early evolution and diversification of Hox-related genes in eumetazoans has been the subject of conflicting hypotheses concerning the evolutionary conservation of their role in axial patterning and the pre-bilaterian origin of the Hox and ParaHox clusters. The diversification of Hox/ParaHox genes clearly predates the origin of bilaterians. However, the existence of a "Hox code' predating the cnidarian-bilaterian ancestor and supporting the deep homology of axes is more controversial. This assumption was mainly based on the interpretation of Hox expression data from the sea anemone, but growing evidence from other cnidarian taxa puts into question this hypothesis. Methodology/Principal Findings: Hox, ParaHox and Hox-related genes have been investigated here by phylogenetic analysis and in situ hybridisation in Clytia hemisphaerica, an hydrozoan species with medusa and polyp stages alternating in the life cycle. Our phylogenetic analyses do not support an origin of ParaHox and Hox genes by duplication of an ancestral ProtoHox cluster, and reveal a diversification of the cnidarian HOX9-14 genes into three groups called A, B, C. Among the 7 examined genes, only those belonging to the HOX9-14 and the CDX groups exhibit a restricted expression along the oralaboral axis during development and in the planula larva, while the others are expressed in very specialised areas at the medusa stage. Conclusions/Significance: Cross species comparison reveals a strong variability of gene expression along the oral-aboral axis and during the life cycle among cnidarian lineages. The most parsimonious interpretation is that the Hox code, collinearity and conservative role along the antero-posterior axis are bilaterian innovations